POSITION STATEMENT * ENONCE DE POSITION
Steroid
therapy
for croup
in
children
Steroid' therapy for croup in children admitted
to hospital
Infectious Diseases and Immunization Committee, Canadian Paediatric Society C roup (acute laryngotracheitis) is one of the most common respiratory tract infections in children 3 months to 3 years of age. It is most commonly caused by a viral infection of the- subglottic area leading to edema and narrowing of the airway. The syndrome is generally self-limited, obstructive symptoms lasting 4 days on average. From 1.5% to 15% of affected children seen as outpatients are admitted to hospital.",2 In hospital 1% to 5% of children with croup require mechanical ventilation.3,4 The therapeutic options for the management of croup include humidified air, oxygen, racemic epinephrine and steroids.5 The role of steroids remains controversial despite its evaluation in more than 14 clinical trials over the past 30 years.6 Many of these trials involved relatively few patients and consequently had insufficient power to measure a small but significant effect.7 Meta-analysis has been used and may provide a better estimate of the effectiveness of steroids in croup.8 The meta-analysis used evidence from clinical trials in which patients admitted to hospital were randomly assigned to a group receiving steroids or a
control group;9-'8 group assignment was unknown to the observer. The outcome measure was clinical improvement at 12 and 24 hours. In most of the trials a croup score was used to measure clinical improvement. This method makes use of a standardized form for quantifying clinical observations such as inspiratory stridor, retractions, air entry, cyanosis and level of consciousness. In seven studies, involving a total of 874 patients, clinical improvement was seen at 12 hours after treatment in 81 % of those in the steroid treatment group as compared with 66% of those in the control group. Similarly, at 24 hours improvement was observed in 96% and 82% respectively. In addition, the meta-analysis showed a dose effect consistent with the hypothesis that a lower dose of steroid is less effective. In nine studies, involving 1126 subjects, eight endotracheal intubations were performed: one (0.17%) in the treatment group and seven (1.27%) in the control group. Neither length of hospital stay nor incidence of adverse effects associated with steroid use was compared in this analysis. After the meta-analysis a small but welldesigned and well-executed study of the effectiveness
Members: Drs. Norman A. Goldberg (director responsible), Children's Hospital, Winnipeg, Man.; Noni E. MacDonald (chairperson), Department ofPaediatrics, Children's Hospital ofEastern Ontario, Ottawa, Ont.; Gilles Delage, Department of Medical Microbiology, H6pital Sainte-Justine, Montreal, Que.; Scott Halperin, Department of Pediatrics, Izaak Walton Killam Hospitalfor Children, Halifax, NS; Taj Jadavji, Department of Paediatrics, Alberta Children's Hospital, Calgary, Alta.; Susan King (principal author), Division of Infectious Diseases, Hospitalfor Sick Children, Toronto, Ont.; Normand Lapointe, Department of Pediatrics, Hopital Sainte-Justine, Montreal, Que.; and Barbara Law, Department ofMedical Microbiology, University of Manitoba, Winnipeg, Man. Consultants: Drs. Ronald Gold, Department ofPediatrics, Hospitalfor Sick Children, Toronto, Ont.; and Victor Marchessault, Department of Paediatrics, Children's Hospital ofEastern Ontario, Ottawa, Ont. Liaisons: American Academy of Pediatrics, Dr. Carol Phillips, Department of Pediatrics, University of Vermont, Burlington, Vt.; Centre for Vaccine Evaluation, Dr. David W. Scheifele, Research Center, British Columbia's Children's Hospital, Vancouver, BC; Comite d'immunisation du Quebec, Dr. Pierre Dery, Department ofPediatrics, Centre hospitalier de l'Universite Laval, Sainte-Foy, Que.; epidemiology, Dr. John R. Waters, Communicable Disease Control and Epidemiology, Alberta Department of Social Services and Community Health, Edmonton, Alta.; and public health, Dr. Jacqueline AK. Carlson, Disease Control and Epidemiology Service, Ontario Ministry ofHealth, Toronto, Ont. Reprint requests to: Infectious Diseases and Immunization Committee, Canadian Paediatric Society, Children's Hospital ofEastern Ontario, 401 Smyth Rd., Ottawa, ON KJH 8LI -
For prescribing information see page 538
CAN MED ASSOC J 1992; 147 (4)
429
of a single parenteral dose of dexamethasone (0.6 mg/kg) was reported by Super and associates.'9 Their results were consistent with those of the meta-analysis: clinical improvement at 12 and 24 hours after treatment was observed in over 80% of the dexamethasone-treated group and in 33% of the control group. The average lengths of stay in hospital for the two groups were 3.6 and 3.0 days respectively. The use of steroids in children with croup who are admitted to hospital increases the likelihood of clinical improvement, as measured by a croup score, at 12 and 24 hours. Such use may also reduce the need for intubation. There is no evidence that steroids will shorten the average length of stay in hospital. The safety of steroid therapy for croup has not been fully evaluated. Although no adverse effects have been reported, the number of patients studied has been too small to detect a serious but uncommon complication such as gastrointestinal bleeding. Severe gastrointestinal bleeding necessitating transfusion was reported in 2 of 102 children with meningitis treated for 4 days with dexamethasone, 0.6 mg/kg daily.20 Careful consideration must be given to the use of any drug in the management of a disease that, in most children, is self-limited and uncomplicated. On the basis of the evidence available we recommend that if a child is admitted to hospital with severe croup, steroid therapy could be used. Dexamethasone, 0.6 mg/kg, should be given in a single parenteral or intramuscular dose.
References 1. Denny FW, Murphy TF, Wallace AC et al: Croup: an 1 -year study in a pediatric practice. Pediatrics 1983; 71: 871-876 2. Stern RC: Infectious croup. In Behrman RE, Vaughn VC (eds): Nelson Textbook of Pediatrics, 12th ed, Saunders,
430
CAN MED ASSOCJ 1992; 147(4)
Philadelphia, 1983: 1034-1038 3. Wagener JS, Landau LI, Olinsky A et al: Management of children hospitalized for laryngotracheobronchitis. Pediatr Pulmonol 1986; 2:159-162 4. Adair JC, Ring WH, Jordan WS et al: Ten-year experience with IPPB in treatment of acute laryngotracheobronchitis. AnesthAnaig 1971; 50: 649-655 5. Skolnik NS: Treatment of croup: a critical review. Am J Dis Child 1989; 143: 1045-1049 6. Smith DS: Corticosteroids in croup: A chink in the ivory tower?JPediatr 1989; 115: 256-257 7. Tunnessen WW, Feinstein AR: The steroid-croup controversy: an analytic review of the methodology problems. J Pediatr 1980; 96: 751-756 8. Kairys SW, Olmstead EM, O'Connor GT: Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics 1989; 83: 683-693 9. Martensson B, Nilson G, Torbjar J: The effect of corticosteroids in the treatment of pseudo-croup. Acta Otolaryngol 1960; 158 (suppl): 62-69 10. Novik A: Corticosteroid treatment of non-diphtheric croup. Acta Otolaryngol 1960; 158 (suppl): 20-23 11. Eden A, Larkin VP: Corticosteroid treatment of croup. Pediatrics 1964; 33: 768-769 12. Sussman S, Grossman M, Magoffin MD et al: Dexamethasone in obstructive respiratory tract infections in children. Pediatrics 1964; 34: 851-855 13. Skowron PN, Turner JAP, McNaughton GA: The use of corticosteroid (dexamethasone) in the treatment of acute laryngotracheitis. Can Med Assoc J 1966; 94: 528-531 14. Eden A, Kaufman A, Yu R: Corticosteroids and croup. JAMA 1967; 200: 133-134 15. James J: Dexamethasone in croup. Am J Dis Child 1969; 117: 511-516 16. Leipzig B, Oski FA: A prospective randomized study to determine the efficacy of steroids in the treatment of croup. J Pediatr 1979; 94: 194-196 17. Muhlendahl KE, Kahn D, Spohr HL et al: Steroid treatment in pseudo-croup. Helv Paediatr Acta 1982; 37: 431-436 18. Koren G, Frand M, Barzilay Z et al: Corticosteroid treatment of laryngotracheitis vs spasmodic croup in children. Am J Dis Child 1983; 137: 941-944 19. Super DM, Cartelli NA, Brooks LJ et al: A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis. J Pediatr 1989; 115: 323-329 20. Lebel MH, Freij BJ, Syrogiannopoulos GA et al: Dexamethasone therapy for bacterial meningitis. N Engl J Med 1988; 319: 964-971
LE 15AOUT 1992
Corticotherapie chez les enfants hospitalisSs Coricotherapie chez les enfants hospitalises pour laryngotracheite aigue (croup)
Comite des maladies infectieuses et d'immunisation, Societe canadienne de pediatrie
L a laryngotracheite aigue (croup) est l'une des infections des voies respiratoires les plus courantes chez les enfants ages de 3 mois a 3 ans. Elle est causee le plus souvent par une infection virale au niveau de la region sous-glottique et provoque de l'oedeme et un retrecissement du conduit aerien. Le syndrome est generalement spontanement resolutif et les symptomes obstructifs persistent en moyenne pendant 4 jours. Entre- 1,5 % et 15 % des enfants atteints et vus en consultation externe sont admis a l'hopital.1"2 Chez les enfants hospitalises pour ce syndrome, 1 % a 5 % auront besoin de ventilation contr6lee.34 Les choix therapeutiques de la prise en charge de la laryngotracheite aigue comprennent l'air humidifie, I'oxygene, I'epinephrine racemique et les steroides.5 Le role des steroides est encore controverse en depit de leur evaluation effectuee dans le cadre d'au moins 14 essais cliniques au cours des 30 dernieres ann6es.6 Plusieurs de ces essais regroupaient relativement peu de patients et n'avaient donc pas l'ampleur suffisante pour mesurer des effets importants quoique minimes.7 La meta-analyse a e utilisee et elle peut fournir une meilleure estimation de l'efficacite des steroides dans le traitement de la laryngotracheite aigue.8 La meta-analyse a utilise les donnees fournis par les essais cliniques: les patients admis a l'hopital etaient assignes au hasard a un groupe recevant des steroides ou a un groupe controle9-'8 et l'assignation
des deux groupes n'etait pas connue de l'observateur. L'indicateur des resultats concluait a une amelioration clinique 12 heures et 24 heures apres le debut du traitement. Dans la majorite des etudes, un
Steroid
therapy
for croup
in
children
Steroid' therapy for croup in children admitted
to hospital
Infectious Diseases and Immunization Committee, Canadian Paediatric Society C roup (acute laryngotracheitis) is one of the most common respiratory tract infections in children 3 months to 3 years of age. It is most commonly caused by a viral infection of the- subglottic area leading to edema and narrowing of the airway. The syndrome is generally self-limited, obstructive symptoms lasting 4 days on average. From 1.5% to 15% of affected children seen as outpatients are admitted to hospital.",2 In hospital 1% to 5% of children with croup require mechanical ventilation.3,4 The therapeutic options for the management of croup include humidified air, oxygen, racemic epinephrine and steroids.5 The role of steroids remains controversial despite its evaluation in more than 14 clinical trials over the past 30 years.6 Many of these trials involved relatively few patients and consequently had insufficient power to measure a small but significant effect.7 Meta-analysis has been used and may provide a better estimate of the effectiveness of steroids in croup.8 The meta-analysis used evidence from clinical trials in which patients admitted to hospital were randomly assigned to a group receiving steroids or a
control group;9-'8 group assignment was unknown to the observer. The outcome measure was clinical improvement at 12 and 24 hours. In most of the trials a croup score was used to measure clinical improvement. This method makes use of a standardized form for quantifying clinical observations such as inspiratory stridor, retractions, air entry, cyanosis and level of consciousness. In seven studies, involving a total of 874 patients, clinical improvement was seen at 12 hours after treatment in 81 % of those in the steroid treatment group as compared with 66% of those in the control group. Similarly, at 24 hours improvement was observed in 96% and 82% respectively. In addition, the meta-analysis showed a dose effect consistent with the hypothesis that a lower dose of steroid is less effective. In nine studies, involving 1126 subjects, eight endotracheal intubations were performed: one (0.17%) in the treatment group and seven (1.27%) in the control group. Neither length of hospital stay nor incidence of adverse effects associated with steroid use was compared in this analysis. After the meta-analysis a small but welldesigned and well-executed study of the effectiveness
Members: Drs. Norman A. Goldberg (director responsible), Children's Hospital, Winnipeg, Man.; Noni E. MacDonald (chairperson), Department ofPaediatrics, Children's Hospital ofEastern Ontario, Ottawa, Ont.; Gilles Delage, Department of Medical Microbiology, H6pital Sainte-Justine, Montreal, Que.; Scott Halperin, Department of Pediatrics, Izaak Walton Killam Hospitalfor Children, Halifax, NS; Taj Jadavji, Department of Paediatrics, Alberta Children's Hospital, Calgary, Alta.; Susan King (principal author), Division of Infectious Diseases, Hospitalfor Sick Children, Toronto, Ont.; Normand Lapointe, Department of Pediatrics, Hopital Sainte-Justine, Montreal, Que.; and Barbara Law, Department ofMedical Microbiology, University of Manitoba, Winnipeg, Man. Consultants: Drs. Ronald Gold, Department ofPediatrics, Hospitalfor Sick Children, Toronto, Ont.; and Victor Marchessault, Department of Paediatrics, Children's Hospital ofEastern Ontario, Ottawa, Ont. Liaisons: American Academy of Pediatrics, Dr. Carol Phillips, Department of Pediatrics, University of Vermont, Burlington, Vt.; Centre for Vaccine Evaluation, Dr. David W. Scheifele, Research Center, British Columbia's Children's Hospital, Vancouver, BC; Comite d'immunisation du Quebec, Dr. Pierre Dery, Department ofPediatrics, Centre hospitalier de l'Universite Laval, Sainte-Foy, Que.; epidemiology, Dr. John R. Waters, Communicable Disease Control and Epidemiology, Alberta Department of Social Services and Community Health, Edmonton, Alta.; and public health, Dr. Jacqueline AK. Carlson, Disease Control and Epidemiology Service, Ontario Ministry ofHealth, Toronto, Ont. Reprint requests to: Infectious Diseases and Immunization Committee, Canadian Paediatric Society, Children's Hospital ofEastern Ontario, 401 Smyth Rd., Ottawa, ON KJH 8LI -
For prescribing information see page 538
CAN MED ASSOC J 1992; 147 (4)
429
of a single parenteral dose of dexamethasone (0.6 mg/kg) was reported by Super and associates.'9 Their results were consistent with those of the meta-analysis: clinical improvement at 12 and 24 hours after treatment was observed in over 80% of the dexamethasone-treated group and in 33% of the control group. The average lengths of stay in hospital for the two groups were 3.6 and 3.0 days respectively. The use of steroids in children with croup who are admitted to hospital increases the likelihood of clinical improvement, as measured by a croup score, at 12 and 24 hours. Such use may also reduce the need for intubation. There is no evidence that steroids will shorten the average length of stay in hospital. The safety of steroid therapy for croup has not been fully evaluated. Although no adverse effects have been reported, the number of patients studied has been too small to detect a serious but uncommon complication such as gastrointestinal bleeding. Severe gastrointestinal bleeding necessitating transfusion was reported in 2 of 102 children with meningitis treated for 4 days with dexamethasone, 0.6 mg/kg daily.20 Careful consideration must be given to the use of any drug in the management of a disease that, in most children, is self-limited and uncomplicated. On the basis of the evidence available we recommend that if a child is admitted to hospital with severe croup, steroid therapy could be used. Dexamethasone, 0.6 mg/kg, should be given in a single parenteral or intramuscular dose.
References 1. Denny FW, Murphy TF, Wallace AC et al: Croup: an 1 -year study in a pediatric practice. Pediatrics 1983; 71: 871-876 2. Stern RC: Infectious croup. In Behrman RE, Vaughn VC (eds): Nelson Textbook of Pediatrics, 12th ed, Saunders,
430
CAN MED ASSOCJ 1992; 147(4)
Philadelphia, 1983: 1034-1038 3. Wagener JS, Landau LI, Olinsky A et al: Management of children hospitalized for laryngotracheobronchitis. Pediatr Pulmonol 1986; 2:159-162 4. Adair JC, Ring WH, Jordan WS et al: Ten-year experience with IPPB in treatment of acute laryngotracheobronchitis. AnesthAnaig 1971; 50: 649-655 5. Skolnik NS: Treatment of croup: a critical review. Am J Dis Child 1989; 143: 1045-1049 6. Smith DS: Corticosteroids in croup: A chink in the ivory tower?JPediatr 1989; 115: 256-257 7. Tunnessen WW, Feinstein AR: The steroid-croup controversy: an analytic review of the methodology problems. J Pediatr 1980; 96: 751-756 8. Kairys SW, Olmstead EM, O'Connor GT: Steroid treatment of laryngotracheitis: a meta-analysis of the evidence from randomized trials. Pediatrics 1989; 83: 683-693 9. Martensson B, Nilson G, Torbjar J: The effect of corticosteroids in the treatment of pseudo-croup. Acta Otolaryngol 1960; 158 (suppl): 62-69 10. Novik A: Corticosteroid treatment of non-diphtheric croup. Acta Otolaryngol 1960; 158 (suppl): 20-23 11. Eden A, Larkin VP: Corticosteroid treatment of croup. Pediatrics 1964; 33: 768-769 12. Sussman S, Grossman M, Magoffin MD et al: Dexamethasone in obstructive respiratory tract infections in children. Pediatrics 1964; 34: 851-855 13. Skowron PN, Turner JAP, McNaughton GA: The use of corticosteroid (dexamethasone) in the treatment of acute laryngotracheitis. Can Med Assoc J 1966; 94: 528-531 14. Eden A, Kaufman A, Yu R: Corticosteroids and croup. JAMA 1967; 200: 133-134 15. James J: Dexamethasone in croup. Am J Dis Child 1969; 117: 511-516 16. Leipzig B, Oski FA: A prospective randomized study to determine the efficacy of steroids in the treatment of croup. J Pediatr 1979; 94: 194-196 17. Muhlendahl KE, Kahn D, Spohr HL et al: Steroid treatment in pseudo-croup. Helv Paediatr Acta 1982; 37: 431-436 18. Koren G, Frand M, Barzilay Z et al: Corticosteroid treatment of laryngotracheitis vs spasmodic croup in children. Am J Dis Child 1983; 137: 941-944 19. Super DM, Cartelli NA, Brooks LJ et al: A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis. J Pediatr 1989; 115: 323-329 20. Lebel MH, Freij BJ, Syrogiannopoulos GA et al: Dexamethasone therapy for bacterial meningitis. N Engl J Med 1988; 319: 964-971
LE 15AOUT 1992
Corticotherapie chez les enfants hospitalisSs Coricotherapie chez les enfants hospitalises pour laryngotracheite aigue (croup)
Comite des maladies infectieuses et d'immunisation, Societe canadienne de pediatrie
L a laryngotracheite aigue (croup) est l'une des infections des voies respiratoires les plus courantes chez les enfants ages de 3 mois a 3 ans. Elle est causee le plus souvent par une infection virale au niveau de la region sous-glottique et provoque de l'oedeme et un retrecissement du conduit aerien. Le syndrome est generalement spontanement resolutif et les symptomes obstructifs persistent en moyenne pendant 4 jours. Entre- 1,5 % et 15 % des enfants atteints et vus en consultation externe sont admis a l'hopital.1"2 Chez les enfants hospitalises pour ce syndrome, 1 % a 5 % auront besoin de ventilation contr6lee.34 Les choix therapeutiques de la prise en charge de la laryngotracheite aigue comprennent l'air humidifie, I'oxygene, I'epinephrine racemique et les steroides.5 Le role des steroides est encore controverse en depit de leur evaluation effectuee dans le cadre d'au moins 14 essais cliniques au cours des 30 dernieres ann6es.6 Plusieurs de ces essais regroupaient relativement peu de patients et n'avaient donc pas l'ampleur suffisante pour mesurer des effets importants quoique minimes.7 La meta-analyse a e utilisee et elle peut fournir une meilleure estimation de l'efficacite des steroides dans le traitement de la laryngotracheite aigue.8 La meta-analyse a utilise les donnees fournis par les essais cliniques: les patients admis a l'hopital etaient assignes au hasard a un groupe recevant des steroides ou a un groupe controle9-'8 et l'assignation
des deux groupes n'etait pas connue de l'observateur. L'indicateur des resultats concluait a une amelioration clinique 12 heures et 24 heures apres le debut du traitement. Dans la majorite des etudes, un
