- Email: [email protected]
Viral croup: a current perspective
ORIGINAL ARTICLE
PH C
Viral Croup: A Current Perspective Alexander K. C. Leung, MBBS, FRCPC, FRCP ( U K & I r e l ) , F R C P C H , Ja m e s D. Ke l l n e r, M D, F R C P C , & D av i d W. Jo h n s o n , M D, F R C P C
V ABSTRACT Viral croup is the most common cause of upper airway obstruction in children 6 months to 6 years of age. Parainfluenza virus accounts for the majority of cases. The disease is characterized by varying degrees of inspiratory stridor, barking cough, and hoarseness because of laryngeal and/or tracheal obstruction. The diagnosis is mainly a clinical one and diagnostic studies usually are not necessary. The management has altered dramatically in the past decade. Good evidence exists to support the routine use of corticosteroid in all children with croup. Intervention at an earlier phase of the illness will reduce the severity of the symptoms and the rates of return to a health care practitioner for additional medical attention, visits to the emergency department, and admission to the hospital. Most children respond to a single, oral dose of dexamethasone. For those who do not tolerate the oral preparation, nebulized budesonide or intramuscular dexamethasone are reasonable alternatives. Nebulized epinephrine should be reserved for patients with moderate to severe croup. Simultaneous administration of corticosteroid and epinephrine reduces the rate of intubation in patients with severe croup and impending respiratory failure. J Pediatr Health Care. (2004). 18, 297-301
November/December 2004
iral croup (laryngotracheobronchitis), a clinical syndrome caused by various viral agents, is characterized by varying degrees of inspiratory stridor, barking cough, and hoarseness as a result of laryngeal and/or tracheal obstruction. The word “croup” is derived from the Anglo-Saxon word kropan which means “to cry aloud” (Cherry, 2004). Croup is one of the most common respiratory illnesses and the most common cause of upper airway obstruction in children 6 months to 6 years of age (Griffin, Ellis, FitzgeraldBarron, Rose, & Egger, 2002). In the majority of cases, the disease is mild and self-limited. Nevertheless, it poses a large burden on the health care systems. Occasionally, it may cause severe respiratory obstruction, and hospitalization rates of 1.3% to 2.6% have been reported (Peltola, Heikkinen, & Ruuskanen, 2002). The management of croup has undergone dramatic changes in the last decade because of our increased awareness of the benefits of steroid treatment. This article reviews the current approach and treatment of croup. ETIOLOGY Parainfluenza virus accounts for more than two thirds of cases of viral croup, with type 1 and 2 responsible for the majority of cases (Malhotra & Krilov, 2001; Peltola et al., 2002). Other etiologic agents include influenza virus, respiratory syncytial virus, metapneumovirus, adenovirus, rhinovirus, enterovirus and, rarely, measles virus and herpes simplex virus (Ewig, 2002; McIntosh & McAdam, 2004). When croup is caused by an influenza virus, the clinical picture is usually more severe than that caused by a parainfluenza virus (Peltola et al., 2002). EPIDEMIOLOGY Croup accounts for approximately 15% of respiratory tract disease seen in
Alexander K. C. Leung is Clinical Associate Professor, Department of Pediatrics, the University of Calgary, and the Alberta Children’s Hospital, Calgary, Alberta, Canada. James D. Kellner is Associate Professor, Department of Pediatrics, the University of Calgary, and the Alberta Children’s Hospital, Calgary, Alberta, Canada. David D. Johnson is Associate Professor, Department of Pediatrics, the University of Calgary, and the Alberta Children’s Hospital, Calgary, Alberta, Canada. Reprint requests: Dr. Alexander K. C. Leung, #200, 233-16th Ave NW, Calgary, Alberta T2M 0H5 Canada; e-mail: [email protected]. 0891-5245/$30.00 Copyright © 2004 by the National Association of Pediatric Nurse Practitioners. doi:10.1016/j.pedhc.2004.08.004
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PH ORIGINAL ARTICLE C the pediatric age group (Cherry, 2004). The condition is most common between the ages of 6 months and 3 years but can occur in children as young as 3 months and as old as 15 years of age; the peak incidence occurs during the second year of life (Thomas & Friedland, 1998). The male to female ratio is approximately 3 to 2 (Knutson & Aring, 2004). The condition is most prevalent in the fall and winter months (Ewig, 2002; Knutson & Aring, 2004). Transmission is by droplets and/or direct contact (Cressman & Myer, 1994). PATHOGENESIS Viral infection of the upper airway results in inflammation and edema of the larynx, trachea, and bronchi and production of mucus that further obstructs the airway. The subglottic trachea is the narrowest part of a child’s upper airway, the narrowing of which results in audible inspiratory stridor (Malhotra & Krilov, 2001). Because of the subglottic trachea is outside the pleural cavity, the negative pressure generated on inspiration tends to narrow the airway further (Hall & Hall, 2001). As the disease progresses, the tracheal lumen becomes further obstructed by fibrous exudates. Swelling of the vocal cord, on the other hand, results in hoarseness of voice. The barking cough is engendered by the inflammation in the larynx and trachea.
CLINICAL MANIFESTATIONS The incubation period is 2 to 6 days (Cressman & Myer, 1994). Viral croup typically is preceded by a prodrome consisting of rhinorrhea, mild cough, and low-grade fever. The duration of the prodrome is usually 12 to 48 hours (Cherry, 2004). The child then develops the characteristic “barking” or “brassy” cough, hoarseness, and inspiratory stridor. Symptoms are characteristically worse at night and are aggravated by agitation and crying (Knutson & Aring, 2004). More than 80% of children have mild symptoms. In approximately 60% to 95% of children, the symptoms resolve within 2 and 5 days, respectively (Johnson & Williamson, 2001). More severe cases may have, in addition, tachycardia; tachypnea; nasal flaring; supraclavicular, infraclavicular, intercostal, and sternal retraction; continuous stridor; and cyanosis. A number of rating scales have been devised to as-
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sess the severity of croup; the most popular and commonly used is the Westley croup score (Table) (Brown, 2002; Powell & Stokell, 2000). The rating scales are of limited value in clinical practice. They are used mainly in research studies to assess treatment outcomes.
DIFFERENTIAL DIAGNOSIS The differential diagnosis of viral croup is listed in the Box. Spasmodic croup usually is not preceded by an upper respiratory tract infection, and there is no associated fever (Leung & Cho, 1999). It often occurs with a sudden onset at night and usually resolves in the morning. Spasmodic croup is recurrent in approximately 5% of children, and there may be a family history of atopy (Van Bever et al., 1999). Epiglottitis tends to occur in older children (2 to 7 years of age). The disease is characterized by an abrupt onset of high fever, toxicity, stridor, dysphagia, and drooling. The child may prefer to sit leaning forward with the mouth open and the tongue somewhat protruding. There is no barky cough.
V
iral croup typically
is preceded by a prodrome consisting of rhinorrhea, mild cough, and low-grade fever.
Epiglottitis is rarely seen nowadays because of the widespread use of Haemophilus influenzae type b vaccine (Leung & Jadavji, 1988). Bacterial tracheitis is usually a superinfection following viral croup but can manifest as a primary infection (Ewig, 2002). The condition can be distinguished from viral croup by the presence of high fever, toxicity, and increasing respiratory distress unresponsive to the conventional treatment for viral croup. Foreign body aspiration may cause acute stridor. A history of recent aspiration or choking on a foreign body can be
TABLE Westley croup scoring system Symptom
Level of consciousness Normal (including sleep) Disoriented Cyanosis None Cyanosis with agitation Cyanosis at rest Stridor None When agitated At rest Air entry Normal Decreased Markedly decreased Retractions None Mild Moderate Severe
Score
0 5 0 4 5 0 1 2 0 1 2 0 1 2 3
Data from Westley, C. R., et al. (1978).
obtained in 90% of cases (Leung & Cho, 1999). The most common symptoms of laryngotracheal foreign bodies are cough, stridor, and dyspnea, whereas those of bronchial foreign bodies are cough, decreased breath sounds, wheezing, and dysphagia (Leung & Cho). In vocal cord paralysis, the stridor typically is biphasic. In unilateral vocal cord paralysis, the infant’s cry is weak and feeble; however, usually there is no respiratory distress. In bilateral vocal cord paralysis, the voice is usually of good quality, but there is marked respiratory distress (Leung & Cho, 1999). Angioneurotic edema may result in acute swelling of the upper airway with resultant stridor and dyspnea. Swelling of the face, tongue, or pharynx also may be present. Rarely, hypocalcemia may cause laryngospasm (hypocalcemic tetany) and stridor. Other features include irritability, tremors, twitchings, and carpopedal spasm. Stridor may be a manifestation of a conversion disorder. Characteristically, the onset of psychogenic stridor is sudden but without the expected amount of distress (Leung & Cho, 1999). The neck often is held in a flexed position rather than in an extended position.
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PH ORIGINAL ARTICLE C DIAGNOSIS The diagnosis of viral croup is mainly a clinical one based on the history and physical findings. Diagnostic studies usually are not necessary. Radiographs of the neck should be considered when aspirated foreign body is suspected, when the diagnosis is in doubt, and when the response to standard treatment is unsatisfactory (Folland, 1997). A “pencil tip” or “steeple sign” of subglottic edema in the anteroposterior view and an overdistended hypopharynx on the lateral view are classical findings in croup (Knutson & Aring, 2004).
MANAGEMENT Treatment depends on the severity of the illness and may include any or all of the following modalities: general supportive measures, corticosteroids, nebulized epinephrine, supplemental oxygen, and endotracheal intubation.
General Supportive Measures It is important to maintain a calm and reassuring atmosphere for the parents and child (Respiratory Committee of the Paediatric Society of New Zealand, 1995). Most children can be managed effectively at home. Antipyretics should be given if the child is febrile. Adequate hydration should be maintained. The use of mist therapy, although traditional, is of unproven value (Bourchier, Dawson, & Fergusson, 1984; Neto, Kentab, Klassen, & Osmond, 2002). At best, it works like a placebo to make the parents feel that they are doing something for the child (Chandler, 2002). At worse, such treatment may be anxiety provoking. Randomized, controlled trials evaluating mist therapy in croup did not demonstrate any benefit in using a humidified atmosphere when compared with room air (Bourchier et al., 1984; Neto et al., 2002). As such, the use of mist therapy is not justified.
Corticosteroids Corticosteroids are the mainstay of therapy for croup. Corticosteroids have potent vasoconstrictive and antiinflammatory properties (Ewig, 2002). Corticosteroids reduce airway inflammation, vascular permeability, and mucosal edema (Malhotra & Krilov, 2001). During the past decade, multiple randomized, placebo-controlled
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trials and meta-analyses have established benefits from corticosteroid treatment with respect to improvement of croup scores, decreased rates of return to the health care practitioner and emergency department for persistent symptoms, reduced length of observation in emergency department, decreased hospitalization rates, shorter hospital stays, and decreased need for more intensive ventilatory support (Ausejo et al., 1999; Osmond, 2002; Rittichier & Ledwith, 2000; Rowe, 2002). Good evidence now exists to support to use of steroids in the management of severe, moderate, or even mild croup (Bjornson et al., 2004; Geelhoed, Turner, & Macdonald, 1996). In a recent multicenter, doubleblind, randomized, placebocontrolled trial of 720 children with mild croup, those treated with dex-
E
piglottitis tends
to occur in older children (2 to 7 years of age). The disease is characterized by an abrupt onset of high fever, toxicity, stridor, dysphagia, and drooling.
amethasone, compared with placebo, had half the rate of return to a health care practitioner (7% versus 15%), more rapid resolution of croup symptoms, less lost sleep, and less parental stress (Bjornson et al.). The most frequently studied corticosteroids are dexamethasone, given orally or intramuscularly, and budesonide, given by nebulization. Dexamethasone is a potent corticosteroid with an anti-inflammatory effect ten times that of prednisone (Folland, 1997; Klassen & Rowe, 1996). Budesonide is a synthetic glucocorticoid with relatively strong topical anti-inflammatory effects and low systemic activity compared
with beclomethasone (Folland). Both systemic dexamethasone (oral or intramuscular) and nebulized budesonide have been found to be equally effective (Ausejo et al., 1999; Geelhoed & Macdonald, 1995; Johnson et al., 1998; Osmond, 2002; Ritticher & Ledwith, 2000; Rowe, 2002). Oral dexamethasone is preferred because it is inexpensive, easy to administer, readily available, and relatively well tolerated (Fitzgerald & Kilham, 2003; Griffin et al., 2002; Klassen et al., 1998). Administering dexamethasone intramuscularly is painful and administration of nebulized budesonide can be distressing. As such, intramuscular dexamethasone or nebulized budesonide should be reserved for children unable or unwilling to take the oral form (Ewig, 2002; Rittichier & Ledwith, 2000). The potential for adverse effects following a single dose of systemic dexamethasone is extremely low, and safety is generally not a issue. However, the medication should be used with caution in children with known immune deficiency or recent exposure to chickenpox (Folland, 1997; Jaffe, 1998; Johnson, 2004). The traditional dose of dexamethasone is 0.6 mg/kg (Johnson, 2004; Malhotra & Krilov, 2001). There is conflicting evidence regarding whether smaller doses of steroid are as effective as the traditional dose. A systematic review found that the higher the dose of corticosteroid administered, the greater the difference in the proportion of children reported to have improvement between the corticosteroid and placebo groups (Geelhoed & MacDonald, 1995). In contrast, a small randomized controlled trial found no significant difference between single oral dexamethasone doses of 0.6 mg/kg versus 0.3 mg/kg versus 0.15 mg/kg in children with mild to moderate croup (Kairys, Olmstead, & O’Connor, 1989). The dosage of nebulized budesonide most frequently used is 2 mg (Ewig, 2002). So far, there have been no published data on whether multiple doses of corticosteroids provide greater benefit than a single dose (Johnson, 2004).
Nebulized Epinephrine Racemic epinephrine is a 1:1 mixture of the dextrorotatory (D) and levorotatory (L) isomers of epinephrine, of which the L form is the active component (Cressman & Myer, 1994; Malho-
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administration of effective doses of corticosteroids and epinephrine.
BOX Differential diagnosis of viral croup Spasmodic croup Epiglottitis Bacterial tracheitis Foreign body Vocal cord paralysis Angioneurotic edema Laryngospasm (hypocalcemic tetany) Psychogenic stridor
CONCLUSION
Modified from Leung & Cho (1999).
tra & Krilov, 2001). Racemic epinephrine works by stimulation of the αadrenergic receptors in the airway with resultant mucosal vasoconstriction and decreased subglottic edema and by stimulation of the β-adrenergic receptors with resultant relaxation of the bronchial smooth muscle (Cressman & Myer; Thomas & Friedland, 1998). Randomized studies comparing racemic epinephrine with either placebo or no treatment have shown significant improvements in croup scores in the treated patients versus the controls (Kristjansson, Berg-Kelly, & Winso, 1994; Ledwith, Shea, & Mauro, 1995). The recommended dose is 0.5 mL of a 2.25% of racemic epinephrine diluted in 2 to 3 mL of normal saline solution (Cressman & Myer; Folland, 1997). L-epinephrine appears equally effective with no additional adverse effects (Waisman et al., 1992). The recommended dose of L-epinephrine is 5 mL of a 1:1,000 solution diluted in 2 to 5 mL of saline solution. The onset of action is 10 to 30 minutes and the duration of action is approximately 2 hours, at which time patients return to their baseline severity. Adverse effects of nebulized epinephrine include tachycardia and circumoral pallor. Although the simultaneous use of corticosteroid helps to reduce the rebound phenomenon and obviates the need for hospitalization, patients still should be observed for a minimum of 2 hours following treatment (Rizos, DiGravio, Sehl, & Tallon, 1998). Nebulized epinephrine should be reserved for children with moderate to severe croup and should be used with caution in children who have tachycardia or ventricular outlet obstruction (Mal-
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hotra & Krilov, 2001). Hospitalization should be considered in children who have stridor at rest with associated chest-wall indrawing after a period of observation (a minimum of 3 hours and optimally 8 to 12 hours).
Supplemental Oxygen Supplemental oxygen should be given for children with significant oxygen desaturation (pulsatile oxygen saturation <90%) (Fitzgerald & Kilham, 2003). Clinically, this is mani-
C
orticosteroids are
the mainstay of therapy for croup.
fested by tachycardia, tachypnea, labored breathing, agitation, cyanosis, and deteriorating clinical state. Children given supplemental oxygen should be monitored by oximetry. The use of a mixture of helium and oxygen may improve ventilation (Malhotra & Krilov, 2001). Helium is an inert, nontoxic, low density gas which can potentially decrease turbulent airflow in a narrow airway (Johnson, 2004). There is, however, insufficient evidence to justify its routine use (Johnson).
Intubation Endotracheal intubation with or without assisted ventilation is rarely required except for those who have impending respiratory failure despite
We advocate that all children diagnosed with croup be treated with corticosteroids. Most children can be treated by health care practitioners with a single, oral dose of dexamethasone on an outpatient basis. Those with moderate involvement may need to be assessed in an emergency department. For those who do not tolerate the oral preparation, nebulized budesonide or intramuscular dexamethasone are reasonable alternatives. Nebulized epinephrine should be reserved for patients with moderate to severe croup. Patients should be observed for a minimum of 2 hours after treatment with epinephrine. Simultaneous administration of corticosteroid with epinephrine reduces both the rate of hospitalization and intubation in patients with severe croup and impending respiratory failure.
ACKNOWLEDGEMENT We thank Ms. Vivian Shiao and Ms. Eudora Cheung for expert secretarial assistance and Mr. Sulakhan Chopra of the University of Calgary Medical Library for help in the preparation of the manuscript.
REFERENCES Ausejo, M., Saenz, A., Pham, B., Kellner, J. D., Johnson, D.W., Moher, D., et al. (1999). The effectiveness of glucocorticoids in treating croup: Meta-analysis. British Medical Journal, 319, 595600. Bjornson, C. L., Klassen, T. P., Williamson, J., Brant, R., Mitton, C., Plint, A., et al. 2004. Treatment of mild croup with a single dose of oral dexamethasone: A multicenter, placebo-controlled trial. The New England Journal of Medicine, 315, 1306-1313. Bourchier, D., Dawson, K. P., & Fergusson, D. M. (1984). Humidification in viral coup: A controlled trial. Australian Paediatric Journal, 20, 289-291. Brown, J. C. (2002). The management of croup. British Medical Bulletin, 61, 189-202. Chandler, T. (2002). Croup. Pediatric Nursing, 14, 41-47. Cherry, J. D. (2004). Croup (laryngitis, laryngotracheitis, spasmodic croup, laryngotracheobronchitis, bacterial tracheitis, and laryngotracheobronchopneumonitis). In R. D. Feigin, J. D. Cherry, G. J. Demmler, & S. L. Kaplan (Eds.), Textbook of pediatric infectious diseases (pp. 252265). Philadelphia: Saunders. Cressman, W. R., & Myer, C. M. III (1994). Diagnosis and management of croup and epiglottitis. Pediatric Clinics of North America, 41, 265-276. Ewig, J. M. (2002). Croup. Pediatric Annals, 31, 125130.
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PH ORIGINAL ARTICLE C Fitzgerald, D. A., & Kilham, H. A. (2003). Croup: Assessment and evidence-based management. Medical Journal of Australia, 179, 372-377. Folland, D. S. (1997). Treatment of croup: Sending home an improved child and relieved parents. Postgraduate Medicine, 101, 271-278. Geelhoed, G. C., & Macdonald, W. B. G. (1995). Oral and inhaled steroids in croup: A randomized, placebo-controlled trial. Pediatric Pulmonology, 20, 355-361. Geelhoed, G. C., Turner, J., & Macdonald W. B. G. (1996). Efficacy of a small single dose of oral dexamethasone for outpatient croup: A double blind placebo controlled clinical trial. British Medical Journal, 313, 140-142. Griffin, S., Ellis, S., Fitzgerald- Barron, A., Rose, J., & Egger, M. (2002). Nebulised steroid in the treatment of croup: A systematic review of randomised controlled trials. British Journal of General Practice, 50, 135-141. Hall, C. B., & Hall, W. J. (2001). Croup (acute laryngotracheobronchitis). In R. A. Hoekelman, H. M. Adam, N. M. Nelson, M. L. Weitzman, & M. H. Wilson (Eds.), Primary pediatric care (pp. 1919-1924). St. Louis: Mosby. Jaffe, D. M. (1998). The treatment of croup with glucocorticoids. New England Journal of Medicine, 339, 553-554. Johnson, D. (2004). How do you know it’s croup? The Canadian Journal of Continuous Medical Education, 16, 40-145. Johnson, D. W., Jacobson, S., Edney, P. C., Hadfield, P., Mundy, M. E., & Schuh, S. (1998). A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. The New England Journal of Medicine, 339, 498-503. Johnson, D. W., & Williamson, J. (2001). Croup: Duration of symptoms and impact on family functioning. Pediatric Research, 49, 83A. Kairys, S. W., Olmstead, E. M., & O’Connor, G. T. (1989). Steroid treatment of laryngotracheitis: A meta-analysis of the evidence from randomized trials. Pediatrics, 83, 683-693. Klassen, T. P., Craig, W. R., Moher, D., Osmond, M.
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H., Pasterkamp, H., Sutcliffe, T., et al. (1998). Nebulized budesonide and oral dexamethasone for treatment of croup: A randomized controlled trial. Journal of the American Medical Association, 279, 1629-1632. Klassen, T. P., & Rowe, P. C. (1996). Outpatient management of croup. Current Opinion in Pediatrics, 8, 449-452. Knutson, D., & Aring, A. (2004). Viral croup. American Family Physician, 69, 535-542. Kristjansson, S., Berg-Kelly, K., & Winso, E. (1994). Inhalation of racemic adrenaline in the treatment of mild and moderately severe croup. Clinical symptom score and oxygen saturation measurements for evaluation of treatment effects. Acta Paediatrica, 83, 1156-1160. Ledwith, C. A., Shea, L. M., & Mauro, R. D. (1995). Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup. Annals of Emergency Medicine, 25, 331-337. Leung, A. K., & Cho, H. (1999). Diagnosis of stridor in children. American Family Physician, 15, 2289-2296. Leung, A. K., & Jadavji, T. (1988). Polysaccharide vaccine for prevention of Haemophilus influenzae type b disease. Journal of the Royal Society of Health, 108, 180-181. Malhotra, A., & Krilov, L. R. (2001). Viral croup. Pediatrics in Review, 22, 5-11. McIntosh, K., & McAdam, A. J. (2004). Human metapneumovirus: An important new respiratory virus. The New England Journal of Medicine, 350, 431-433. Neto, G. M., Kentab, O., Klassen, T. P., & Osmond, M. H. (2002). A randomized controlled trial of mist in the acute treatment of moderate croup. Academic Emergency Medicine, 9, 873-879. Osmond, M. (2002). Croup. Clinical Evidence, 7, 297-306. Peltola, V., Heikkinen, T., & Ruuskanen, O. (2002). Clinical courses of croup caused by influenza and parainfluenza virus. The Pediatric Infectious Disease Journal, 21, 76-78.
Powell, C. V. E., & Stokell, R. A. (2000). Changing hospital management of croup: What does this mean for general practice? Australian Family Physician, 29, 915-919. Respiratory Committee of the Paediatric Society of New Zealand (1995). The management of acute viral croup. New Zealand Medical Jounal, 108, 484-486. Rittichier, K. K., & Ledwith, C. A. (2000). Outpatient treatment of moderate croup with dexamethasone: Intramuscular versus oral dosing. Pediatrics, 106, 1344-1348. Rizos, J. D., DiGravio, B. E., Sehl, M. J., & Tallon, J. M. (1998). The disposition of children with croup treated with racemic epinephrine and dexamethasone in the emergency department. The Journal of Emergency Medicine, 16, 535-539. Rowe, B. H. (2002). Corticosteroid treatment for acute croup. Annals of Emergency Medicine, 40, 353-355. Thomas, L. P., & Friedland, L. R. (1998). The costeffective use of nebulized racemic epinephrine in the treatment of croup. American Journal of Emergency Medicine, 16, 87-89. Van Bever, H. P., Wieringa, M. H., Weyler, J. J., Nelen, V. J., Fortuin, M., & Vermeire, P. A. (1999). Croup and recurrent croup: Their association with asthma and allergy. An epidemiological study on 5-8-year-old children. European Journal of Pediatrics, 158, 253-257. Waisman, Y., Klein, B. L., Boenning, D. A., Young, G. M., Chamberlain, J. M., O’Donnell, R., et al. (1992). Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of larynotracheitis (croup). Pediatrics, 89, 302-306. Westley, C. R., Cotton, E. K., & Brooks, J. G. (1978). Nebulised racemic epinephrine by IPPB for the treatment of croup: A double blind study. American Journal of Diseases of Children, 132, 484-487.
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Viral Croup: A Current Perspective Alexander K. C. Leung, MBBS, FRCPC, FRCP ( U K & I r e l ) , F R C P C H , Ja m e s D. Ke l l n e r, M D, F R C P C , & D av i d W. Jo h n s o n , M D, F R C P C
V ABSTRACT Viral croup is the most common cause of upper airway obstruction in children 6 months to 6 years of age. Parainfluenza virus accounts for the majority of cases. The disease is characterized by varying degrees of inspiratory stridor, barking cough, and hoarseness because of laryngeal and/or tracheal obstruction. The diagnosis is mainly a clinical one and diagnostic studies usually are not necessary. The management has altered dramatically in the past decade. Good evidence exists to support the routine use of corticosteroid in all children with croup. Intervention at an earlier phase of the illness will reduce the severity of the symptoms and the rates of return to a health care practitioner for additional medical attention, visits to the emergency department, and admission to the hospital. Most children respond to a single, oral dose of dexamethasone. For those who do not tolerate the oral preparation, nebulized budesonide or intramuscular dexamethasone are reasonable alternatives. Nebulized epinephrine should be reserved for patients with moderate to severe croup. Simultaneous administration of corticosteroid and epinephrine reduces the rate of intubation in patients with severe croup and impending respiratory failure. J Pediatr Health Care. (2004). 18, 297-301
November/December 2004
iral croup (laryngotracheobronchitis), a clinical syndrome caused by various viral agents, is characterized by varying degrees of inspiratory stridor, barking cough, and hoarseness as a result of laryngeal and/or tracheal obstruction. The word “croup” is derived from the Anglo-Saxon word kropan which means “to cry aloud” (Cherry, 2004). Croup is one of the most common respiratory illnesses and the most common cause of upper airway obstruction in children 6 months to 6 years of age (Griffin, Ellis, FitzgeraldBarron, Rose, & Egger, 2002). In the majority of cases, the disease is mild and self-limited. Nevertheless, it poses a large burden on the health care systems. Occasionally, it may cause severe respiratory obstruction, and hospitalization rates of 1.3% to 2.6% have been reported (Peltola, Heikkinen, & Ruuskanen, 2002). The management of croup has undergone dramatic changes in the last decade because of our increased awareness of the benefits of steroid treatment. This article reviews the current approach and treatment of croup. ETIOLOGY Parainfluenza virus accounts for more than two thirds of cases of viral croup, with type 1 and 2 responsible for the majority of cases (Malhotra & Krilov, 2001; Peltola et al., 2002). Other etiologic agents include influenza virus, respiratory syncytial virus, metapneumovirus, adenovirus, rhinovirus, enterovirus and, rarely, measles virus and herpes simplex virus (Ewig, 2002; McIntosh & McAdam, 2004). When croup is caused by an influenza virus, the clinical picture is usually more severe than that caused by a parainfluenza virus (Peltola et al., 2002). EPIDEMIOLOGY Croup accounts for approximately 15% of respiratory tract disease seen in
Alexander K. C. Leung is Clinical Associate Professor, Department of Pediatrics, the University of Calgary, and the Alberta Children’s Hospital, Calgary, Alberta, Canada. James D. Kellner is Associate Professor, Department of Pediatrics, the University of Calgary, and the Alberta Children’s Hospital, Calgary, Alberta, Canada. David D. Johnson is Associate Professor, Department of Pediatrics, the University of Calgary, and the Alberta Children’s Hospital, Calgary, Alberta, Canada. Reprint requests: Dr. Alexander K. C. Leung, #200, 233-16th Ave NW, Calgary, Alberta T2M 0H5 Canada; e-mail: [email protected]. 0891-5245/$30.00 Copyright © 2004 by the National Association of Pediatric Nurse Practitioners. doi:10.1016/j.pedhc.2004.08.004
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PH ORIGINAL ARTICLE C the pediatric age group (Cherry, 2004). The condition is most common between the ages of 6 months and 3 years but can occur in children as young as 3 months and as old as 15 years of age; the peak incidence occurs during the second year of life (Thomas & Friedland, 1998). The male to female ratio is approximately 3 to 2 (Knutson & Aring, 2004). The condition is most prevalent in the fall and winter months (Ewig, 2002; Knutson & Aring, 2004). Transmission is by droplets and/or direct contact (Cressman & Myer, 1994). PATHOGENESIS Viral infection of the upper airway results in inflammation and edema of the larynx, trachea, and bronchi and production of mucus that further obstructs the airway. The subglottic trachea is the narrowest part of a child’s upper airway, the narrowing of which results in audible inspiratory stridor (Malhotra & Krilov, 2001). Because of the subglottic trachea is outside the pleural cavity, the negative pressure generated on inspiration tends to narrow the airway further (Hall & Hall, 2001). As the disease progresses, the tracheal lumen becomes further obstructed by fibrous exudates. Swelling of the vocal cord, on the other hand, results in hoarseness of voice. The barking cough is engendered by the inflammation in the larynx and trachea.
CLINICAL MANIFESTATIONS The incubation period is 2 to 6 days (Cressman & Myer, 1994). Viral croup typically is preceded by a prodrome consisting of rhinorrhea, mild cough, and low-grade fever. The duration of the prodrome is usually 12 to 48 hours (Cherry, 2004). The child then develops the characteristic “barking” or “brassy” cough, hoarseness, and inspiratory stridor. Symptoms are characteristically worse at night and are aggravated by agitation and crying (Knutson & Aring, 2004). More than 80% of children have mild symptoms. In approximately 60% to 95% of children, the symptoms resolve within 2 and 5 days, respectively (Johnson & Williamson, 2001). More severe cases may have, in addition, tachycardia; tachypnea; nasal flaring; supraclavicular, infraclavicular, intercostal, and sternal retraction; continuous stridor; and cyanosis. A number of rating scales have been devised to as-
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sess the severity of croup; the most popular and commonly used is the Westley croup score (Table) (Brown, 2002; Powell & Stokell, 2000). The rating scales are of limited value in clinical practice. They are used mainly in research studies to assess treatment outcomes.
DIFFERENTIAL DIAGNOSIS The differential diagnosis of viral croup is listed in the Box. Spasmodic croup usually is not preceded by an upper respiratory tract infection, and there is no associated fever (Leung & Cho, 1999). It often occurs with a sudden onset at night and usually resolves in the morning. Spasmodic croup is recurrent in approximately 5% of children, and there may be a family history of atopy (Van Bever et al., 1999). Epiglottitis tends to occur in older children (2 to 7 years of age). The disease is characterized by an abrupt onset of high fever, toxicity, stridor, dysphagia, and drooling. The child may prefer to sit leaning forward with the mouth open and the tongue somewhat protruding. There is no barky cough.
V
iral croup typically
is preceded by a prodrome consisting of rhinorrhea, mild cough, and low-grade fever.
Epiglottitis is rarely seen nowadays because of the widespread use of Haemophilus influenzae type b vaccine (Leung & Jadavji, 1988). Bacterial tracheitis is usually a superinfection following viral croup but can manifest as a primary infection (Ewig, 2002). The condition can be distinguished from viral croup by the presence of high fever, toxicity, and increasing respiratory distress unresponsive to the conventional treatment for viral croup. Foreign body aspiration may cause acute stridor. A history of recent aspiration or choking on a foreign body can be
TABLE Westley croup scoring system Symptom
Level of consciousness Normal (including sleep) Disoriented Cyanosis None Cyanosis with agitation Cyanosis at rest Stridor None When agitated At rest Air entry Normal Decreased Markedly decreased Retractions None Mild Moderate Severe
Score
0 5 0 4 5 0 1 2 0 1 2 0 1 2 3
Data from Westley, C. R., et al. (1978).
obtained in 90% of cases (Leung & Cho, 1999). The most common symptoms of laryngotracheal foreign bodies are cough, stridor, and dyspnea, whereas those of bronchial foreign bodies are cough, decreased breath sounds, wheezing, and dysphagia (Leung & Cho). In vocal cord paralysis, the stridor typically is biphasic. In unilateral vocal cord paralysis, the infant’s cry is weak and feeble; however, usually there is no respiratory distress. In bilateral vocal cord paralysis, the voice is usually of good quality, but there is marked respiratory distress (Leung & Cho, 1999). Angioneurotic edema may result in acute swelling of the upper airway with resultant stridor and dyspnea. Swelling of the face, tongue, or pharynx also may be present. Rarely, hypocalcemia may cause laryngospasm (hypocalcemic tetany) and stridor. Other features include irritability, tremors, twitchings, and carpopedal spasm. Stridor may be a manifestation of a conversion disorder. Characteristically, the onset of psychogenic stridor is sudden but without the expected amount of distress (Leung & Cho, 1999). The neck often is held in a flexed position rather than in an extended position.
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PH ORIGINAL ARTICLE C DIAGNOSIS The diagnosis of viral croup is mainly a clinical one based on the history and physical findings. Diagnostic studies usually are not necessary. Radiographs of the neck should be considered when aspirated foreign body is suspected, when the diagnosis is in doubt, and when the response to standard treatment is unsatisfactory (Folland, 1997). A “pencil tip” or “steeple sign” of subglottic edema in the anteroposterior view and an overdistended hypopharynx on the lateral view are classical findings in croup (Knutson & Aring, 2004).
MANAGEMENT Treatment depends on the severity of the illness and may include any or all of the following modalities: general supportive measures, corticosteroids, nebulized epinephrine, supplemental oxygen, and endotracheal intubation.
General Supportive Measures It is important to maintain a calm and reassuring atmosphere for the parents and child (Respiratory Committee of the Paediatric Society of New Zealand, 1995). Most children can be managed effectively at home. Antipyretics should be given if the child is febrile. Adequate hydration should be maintained. The use of mist therapy, although traditional, is of unproven value (Bourchier, Dawson, & Fergusson, 1984; Neto, Kentab, Klassen, & Osmond, 2002). At best, it works like a placebo to make the parents feel that they are doing something for the child (Chandler, 2002). At worse, such treatment may be anxiety provoking. Randomized, controlled trials evaluating mist therapy in croup did not demonstrate any benefit in using a humidified atmosphere when compared with room air (Bourchier et al., 1984; Neto et al., 2002). As such, the use of mist therapy is not justified.
Corticosteroids Corticosteroids are the mainstay of therapy for croup. Corticosteroids have potent vasoconstrictive and antiinflammatory properties (Ewig, 2002). Corticosteroids reduce airway inflammation, vascular permeability, and mucosal edema (Malhotra & Krilov, 2001). During the past decade, multiple randomized, placebo-controlled
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trials and meta-analyses have established benefits from corticosteroid treatment with respect to improvement of croup scores, decreased rates of return to the health care practitioner and emergency department for persistent symptoms, reduced length of observation in emergency department, decreased hospitalization rates, shorter hospital stays, and decreased need for more intensive ventilatory support (Ausejo et al., 1999; Osmond, 2002; Rittichier & Ledwith, 2000; Rowe, 2002). Good evidence now exists to support to use of steroids in the management of severe, moderate, or even mild croup (Bjornson et al., 2004; Geelhoed, Turner, & Macdonald, 1996). In a recent multicenter, doubleblind, randomized, placebocontrolled trial of 720 children with mild croup, those treated with dex-
E
piglottitis tends
to occur in older children (2 to 7 years of age). The disease is characterized by an abrupt onset of high fever, toxicity, stridor, dysphagia, and drooling.
amethasone, compared with placebo, had half the rate of return to a health care practitioner (7% versus 15%), more rapid resolution of croup symptoms, less lost sleep, and less parental stress (Bjornson et al.). The most frequently studied corticosteroids are dexamethasone, given orally or intramuscularly, and budesonide, given by nebulization. Dexamethasone is a potent corticosteroid with an anti-inflammatory effect ten times that of prednisone (Folland, 1997; Klassen & Rowe, 1996). Budesonide is a synthetic glucocorticoid with relatively strong topical anti-inflammatory effects and low systemic activity compared
with beclomethasone (Folland). Both systemic dexamethasone (oral or intramuscular) and nebulized budesonide have been found to be equally effective (Ausejo et al., 1999; Geelhoed & Macdonald, 1995; Johnson et al., 1998; Osmond, 2002; Ritticher & Ledwith, 2000; Rowe, 2002). Oral dexamethasone is preferred because it is inexpensive, easy to administer, readily available, and relatively well tolerated (Fitzgerald & Kilham, 2003; Griffin et al., 2002; Klassen et al., 1998). Administering dexamethasone intramuscularly is painful and administration of nebulized budesonide can be distressing. As such, intramuscular dexamethasone or nebulized budesonide should be reserved for children unable or unwilling to take the oral form (Ewig, 2002; Rittichier & Ledwith, 2000). The potential for adverse effects following a single dose of systemic dexamethasone is extremely low, and safety is generally not a issue. However, the medication should be used with caution in children with known immune deficiency or recent exposure to chickenpox (Folland, 1997; Jaffe, 1998; Johnson, 2004). The traditional dose of dexamethasone is 0.6 mg/kg (Johnson, 2004; Malhotra & Krilov, 2001). There is conflicting evidence regarding whether smaller doses of steroid are as effective as the traditional dose. A systematic review found that the higher the dose of corticosteroid administered, the greater the difference in the proportion of children reported to have improvement between the corticosteroid and placebo groups (Geelhoed & MacDonald, 1995). In contrast, a small randomized controlled trial found no significant difference between single oral dexamethasone doses of 0.6 mg/kg versus 0.3 mg/kg versus 0.15 mg/kg in children with mild to moderate croup (Kairys, Olmstead, & O’Connor, 1989). The dosage of nebulized budesonide most frequently used is 2 mg (Ewig, 2002). So far, there have been no published data on whether multiple doses of corticosteroids provide greater benefit than a single dose (Johnson, 2004).
Nebulized Epinephrine Racemic epinephrine is a 1:1 mixture of the dextrorotatory (D) and levorotatory (L) isomers of epinephrine, of which the L form is the active component (Cressman & Myer, 1994; Malho-
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administration of effective doses of corticosteroids and epinephrine.
BOX Differential diagnosis of viral croup Spasmodic croup Epiglottitis Bacterial tracheitis Foreign body Vocal cord paralysis Angioneurotic edema Laryngospasm (hypocalcemic tetany) Psychogenic stridor
CONCLUSION
Modified from Leung & Cho (1999).
tra & Krilov, 2001). Racemic epinephrine works by stimulation of the αadrenergic receptors in the airway with resultant mucosal vasoconstriction and decreased subglottic edema and by stimulation of the β-adrenergic receptors with resultant relaxation of the bronchial smooth muscle (Cressman & Myer; Thomas & Friedland, 1998). Randomized studies comparing racemic epinephrine with either placebo or no treatment have shown significant improvements in croup scores in the treated patients versus the controls (Kristjansson, Berg-Kelly, & Winso, 1994; Ledwith, Shea, & Mauro, 1995). The recommended dose is 0.5 mL of a 2.25% of racemic epinephrine diluted in 2 to 3 mL of normal saline solution (Cressman & Myer; Folland, 1997). L-epinephrine appears equally effective with no additional adverse effects (Waisman et al., 1992). The recommended dose of L-epinephrine is 5 mL of a 1:1,000 solution diluted in 2 to 5 mL of saline solution. The onset of action is 10 to 30 minutes and the duration of action is approximately 2 hours, at which time patients return to their baseline severity. Adverse effects of nebulized epinephrine include tachycardia and circumoral pallor. Although the simultaneous use of corticosteroid helps to reduce the rebound phenomenon and obviates the need for hospitalization, patients still should be observed for a minimum of 2 hours following treatment (Rizos, DiGravio, Sehl, & Tallon, 1998). Nebulized epinephrine should be reserved for children with moderate to severe croup and should be used with caution in children who have tachycardia or ventricular outlet obstruction (Mal-
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hotra & Krilov, 2001). Hospitalization should be considered in children who have stridor at rest with associated chest-wall indrawing after a period of observation (a minimum of 3 hours and optimally 8 to 12 hours).
Supplemental Oxygen Supplemental oxygen should be given for children with significant oxygen desaturation (pulsatile oxygen saturation <90%) (Fitzgerald & Kilham, 2003). Clinically, this is mani-
C
orticosteroids are
the mainstay of therapy for croup.
fested by tachycardia, tachypnea, labored breathing, agitation, cyanosis, and deteriorating clinical state. Children given supplemental oxygen should be monitored by oximetry. The use of a mixture of helium and oxygen may improve ventilation (Malhotra & Krilov, 2001). Helium is an inert, nontoxic, low density gas which can potentially decrease turbulent airflow in a narrow airway (Johnson, 2004). There is, however, insufficient evidence to justify its routine use (Johnson).
Intubation Endotracheal intubation with or without assisted ventilation is rarely required except for those who have impending respiratory failure despite
We advocate that all children diagnosed with croup be treated with corticosteroids. Most children can be treated by health care practitioners with a single, oral dose of dexamethasone on an outpatient basis. Those with moderate involvement may need to be assessed in an emergency department. For those who do not tolerate the oral preparation, nebulized budesonide or intramuscular dexamethasone are reasonable alternatives. Nebulized epinephrine should be reserved for patients with moderate to severe croup. Patients should be observed for a minimum of 2 hours after treatment with epinephrine. Simultaneous administration of corticosteroid with epinephrine reduces both the rate of hospitalization and intubation in patients with severe croup and impending respiratory failure.
ACKNOWLEDGEMENT We thank Ms. Vivian Shiao and Ms. Eudora Cheung for expert secretarial assistance and Mr. Sulakhan Chopra of the University of Calgary Medical Library for help in the preparation of the manuscript.
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