When it comes to croup, making the diagnosis is usually easy; deciding how to treat the child may not be. The authors bring order to a sometimes perplexing situation.
When it comes to croup, making the diagnosis is usually easy; deciding how to treat the child may not be. Is drug therapy justified in mild disease? When are steroids appropriate? The authors bring order to a sometimes perplexing situation.
It echoes from the waiting room: That distinctive cough heralding the arrival of a miserable child and miserable parents, exhausted from lack of sleep. Jack, your 2-year-old patient, has had symptoms of a "cold" for two days. He spent last night awake, "barking like a seal," his parents report. Your patient and his family need help. To decide on the best treatment strategy for Jack, you must be certain the diagnosis is croup, evaluate its severity, and decide if he needs treatment and, if so, what agent would be best.
After reviewing this article the physician should be able to:
Diagnose croup during the office visit and rule out the components of the differential diagnosis by identifying the condition's distinctive clinical and epidemiologic characteristics.
Select the most appropriate treatments for mild, moderate, and severe croup, including hospitalization for the most serious cases.
Understand the evidence for the potential efficacy of corticosteroids for treating mild croup, and decide whether this experimental intervention is appropriate in selected patients.
Croup (acute laryngotracheobronchitis) is common in young children. Clinically, it is characterized by a distinctive so-called barking cough that is often accompanied by a hoarse voice. In more severe cases, children have inspiratory stridor and respiratory distress. These symptoms result from varying degrees of airway obstruction.1 Severity ranges from mild, self-limited illness, marked mainly by that barking cough, to severe airway obstruction requiring endotracheal intubation and intensive care management.
Croup usually results from a viral infection of the subglottic area of the upper airway that causes acute inflammation and edema. The child's airway has unique features that predispose it to obstruction. First, because a child's airway is proportionately smaller than that of an adult, a given amount of luminal swelling reduces the diameter of the child's airway much more than in an adult (see the illustration above). Second, the narrowest segment of the child's airway is in the subglottic region at the cricoid cartilage, where swelling and inflammation in croup are prominent.1
Parainfluenza virus types 1 and 3 are isolated in approximately 80% of culture-positive patients with croup.2 Other etiologic agents have been identified, including adenovirus, influenza virus A and B, parainfluenza virus type 2, respiratory syncytial virus, and measles virus and Mycoplasma pneumoniae (both rare causes).
Clinicians traditionally have divided croup into two broad categories: spasmodic croup and laryngotracheobronchitis. Spasmodic croup begins abruptly, generally occurs at night, and often has a milder course than laryngotracheobronchitis. The child may or may not have a history of upper respiratory tract infection. One theory is that spasmodic croup is caused by an allergy to viral antigens.
Laryngotracheobronchitis is more likely than spasmodic croup to arise after upper respiratory tract infection. Like spasmodic croup, it mainly occurs at night and can range from mild to progressive and severe. Both spasmodic croup and laryngotracheobronchitis are seen primarily in children 1 to 6 years of age, and both have been associated with the same respiratory viruses. Although the terminology of these two types of croup has been used for a long time, no convincing evidence exists to indicate that these conditions are, in fact, distinct. Rather, it is likely that spasmodic croup and laryngotracheobronchitis exist on a continuum of clinical presentation of the same disease.1
Croup occurs year round but reliably peaks in late autumn and early winter (Figure 1).3 The disease accounts for a significant percentage of pediatric outpatient visits. The highest incidence is among 2-year-olds, approximately 5% of whom have croup each year.3 By 6 years of age, incidence drops to less than 0.5% a year. Although croup is identified with younger children, it is also diagnosed in older children and adolescents. Croup is diagnosed in boys approximately 40% more often than in girls.4
The great majority of children with croup show only mild symptoms; their parents may not even seek medical care for them. In a somewhat smaller group of children, parents seek medical care at the pediatrician's or other physician's office, or at an emergency department (ED).
Within that latter group, severity of illness varies widely: Some children have no or minimal symptoms (other than the barking cough) and do not require treatment; others, with moderate symptoms, should be treated but are stable and can be returned or discharged home; and far fewer have severe croup and require urgent treatment and admission to the hospital. Of children who are admitted (1.5% to 15% of those who are seen in an outpatient setting), a small percentage require treatment in an ICU. Between 1% and 5% of children hospitalized with croup need endotracheal intubation for airway management.1 (See the "The croup pyramid" above for a view at a glance of this hierarchy of severity.)
The Westley croup score is a clinical instrument that has been used in either its original or a modified form in many randomized clinical trials.512 The score incorporates assessments of a child's level of consciousness, cyanosis, stridor, air entry, and intercostal retractions in determining the severity of airway obstruction. Although it may be impractical to use the full score in practice, its components emphasize clinical characteristics that are extremely valuable in assessing the severity of airway obstruction in a child with croup (see the table below).
Alert and comfortable
Normal breath sounds
Ranges from no stridor to soft stridor at rest
Breath sounds normal or mildly decreased
Easily audible stridor at rest
Agitation or lethargy
Chest wall indrawing
Significantly decreased breath sounds
The duration of symptoms of croup varies. General pediatric textbooks note that symptoms tend to be worse at night and often recur for several days.13 Individual attacks may last a few hours or as long as a week, although this estimate may be based on experience with children who have been hospitalized with more severe disease. A prospective study of children who were given a diagnosis of croup in the ED of a tertiary care children's hospital showed that the median duration of obstructive symptoms was 48 hours (Figure 2). Of the 301 children in whom complete follow-up was possible, 72% had received treatment with dexamethasone. We suspect that the duration of obstructive symptoms would have been longer had the children not been treated (Johnson D, personal communication, September 2001).
More than so-called hard outcome measuresED returns, hospital admissions, length of stayshould be used to determine the benefit of treatment, however. Some "softer," yet important, issues should also be examined. For example, do persistent croup symptoms after discharge place a significant burden on the child and the family? The literature does not answer this question adequately; the answer, when it does come, may provide clinicians with a rational basis for deciding whether drug therapy is justifiable in children with milder disease. Until such data are available, we must rely on the evidence of randomized clinical trials of steroid treatment in moderate or severe croup in deciding how to treat mild croup.
The barking cough of croup is distinctive and usually easily recognized by parents and clinicians. The diagnosis is, therefore, generally straightforward. Although the great majority of children with acute onset of inspiratory airway obstruction have croup, due care must be taken during the history and physical examination to exclude other potentially serious or life-threatening problems (see "A perilous differential diagnosis," below).
Once you are certain the diagnosis is croup, the next task is to decide on the best treatment for that child. In general, treatment for croup has included mist, oxygen, inhaled epinephrine, and steroids.1,14
Mist therapy has interesting historical roots. Its use in hospitals began more than a century ago after parents observed that steam from a kettle or tub seemed to alleviate coughing spasms in their children. The use of mist has slowly begun to fall out of favor in the ED, however, as little evidence exists that it is beneficial.1417 At least one investigator suggested that it is the close physical proximity of the parent while she or he holds the child near the steam that reassures and calms the child, reducing respiratory distress.15 After the ED of the Princess Margaret Hospital for Children in Perth, Australia, stopped using mist to treat croup, no change was seen in the number of children admitted with croup, the numbers of ICU admissions, or the length of hospital stay.18
Mist therapy also presents safety issues. Placing a child in respiratory distress inside a tent makes it more difficult to observe and assess him. In addition, separating the child from his parents often exacerbates anxiety and, in turn, respiratory distress. Nevertheless, as with many therapies that have been used for years, some clinicians may find it difficult to abandon mist therapy.
Oxygen should be supplied in a nonthreatening manner if evidence of cyanosis is present or a low oxygen saturation is observed.
Nebulized epinephrine results in rapid amelioration of moderate and severe obstructive symptoms, but its effects last for only one or two hours.5 Because of concerns about the potential dangers of nebulized epinephrine, as recently as the 1970s the drug was used most often in the ICU. As evidence of the benefits and safety of nebulized epinephrine accumulated over the past two decades, however, epinephrine for croup has emerged from the ICU and is now commonly used on outpatient and inpatient wards. Because the effect of epinephrine is short-lived and does not alter the natural history of the disease,5 we believe it is not of benefit in a child who is asymptomatic (other than the cough) or in one who has only mild symptoms and is otherwise happy and comfortable. It is, however, extremely useful in relieving acute obstructive symptoms in a child with moderate or severe croup.
Initial concerns about a potential rebound effect after administration of nebulized epinephrine have proved unfounded. Children generally show improvement or, at worst, a return to baseline two to four hours after administration.5 In a landmark paper, Westley and colleagues found that racemic ephinephrine caused clinical improvement 10 and 30 minutes after administration. No differences were seen between ephinephrine and placebo two hours after administration, however.5 Observation periods of from one to three hours, before discharge from the ED, have been advocated. No large prospective study has confirmed the ideal duration of observation, although the well-documented duration of the effect of nebulized epinephrine suggests that two to three hours is sufficient. Factors that may warrant a longer period of observation include the severity of the child's airway obstruction on initial assessment and the time of presentation. As croup tends to be worse at night, a child who has significant symptoms early in the evening could be expected to take a turn for the worst later. A past history of severe croup, congenital stridor, or a history of previous airway trauma may also suggest a longer observation period. Of course, social circumstances are an important consideration, especially if a family lives a long distance from medical care or parental judgment about the need to return for care is questionable. If the child needs more than one dose of racemic epinephrine, consider admission to an ICU, hospital ward, or holding unit for further observation.
At our hospital, we use 0.5 mL of racemic epinephrine (2.25% solution) mixed with 2.5 mL of normal saline for nebulization. When using L-epinephrine (1:1000 solution), which sometimes is more readily available, we recommend a dose of 5 mL. We use the same dosage in all children. Because much of the medication escapes through the sides of the nebulizer mask, and because children's tidal breaths are in proportion to their weight, we have adopted a one-size-fits-all philosophy to simplify treatment.
After many years of controversy and discussion in the medical literature, steroids are now widely accepted as capable of reducing the overall severity and duration of respiratory distress associated with moderate and severe croup. Several well-designed studies have shown a clear benefit in outcome, compared with placebo, among children with moderate or severe croup who are treated with an inhaled, oral, or intramuscular steroid. Clinical croup score, number of treatments required with racemic epinephrine, and length of stay in the ED all showed improvement.6,8,11 In addition, the overall rate of hospitalization, total ICU days, and number of children requiring intubation were reduced.6,8,14,18
Two meta-analyses of randomized, controlled trials have been published. One, which examined 10 randomized controlled trials of 1,286 patients, determined that steroids for children hospitalized with croup are associated with a significant increase in the percentage of children who show clinical improvement at 12 and 24 hours after treatment.19 The authors of this meta-analysis also found evidence for a significant reduction in the percentage of children who require endotracheal intubation after steroid therapy.
The second meta-analysisof 24 randomized, controlled trialsfound that steroid treatment was associated with an improvement in the croup score at 6, 12, and 24 hours, a decrease in the number of epinephrine treatments, a decrease in the time spent in the ED, and an average reduction in hospital stay of 16 hours.20 Although these authors found some evidence of publication bias (the possibility that studies with neutral or negative results never reached publication), they concluded that the safety and low cost of dexamethasone justifies its continued use for this indication.
In 1992, based on the results of a well-designed clinical trial and meta-analysis of the literature, the Canadian Pediatric Society issued a statement concluding that steroid therapy (dexamethasone, 0.6mg/kg of body weight, as a single intramuscular or oral dose) be considered in all children who are hospitalized because of croup.11,19,21 In 1994, the American Academy of Pediatrics published a similar message in its Red Book.22
Some evidence shows that children who have mild croup also benefit from treatment with steroids. In a small (48 children in each group), placebo-controlled, randomized clinical trial, one dose of oral dexamethasone (0.15 mg/kg of body weight) was administered to children with mild croup who were seen in an ED. Children treated with an oral steroid had a lower rate of return (0%) for care with problems related to croup than those who received placebo (15%).23
These are impressive results, but we cannot recommend that every child with mild croup receive steroid therapy based on one trialeven though we suspect that future studies in this population may demonstrate a convincing overall benefit to treating mild croup. Some physicians already prescribe a single dose of dexamethasone for patients with mild croup, based on their clinical experience and interpretation of the evidence. Future clinical trials should address this issue by demonstrating whether symptoms resolve more rapidly in these children after treatment, thereby reducing disruption in the life of the patient and his family.
Although treating children who have croup with steroids is generally safe, theoretical concerns exist. First, a child treated with a steroid after exposure to varicella virus may be at increased risk of developing complications of varicella, such as disseminated disease or bacterial superinfection. Published case-control studies addressing this question have yielded conflicting results: One study demonstrated an increase in the risk of complicated varicella in immunocompetent children treated with steroids24; another did not.25 It seems extremely unlikely that a single dose of a steroid in an otherwise healthy child with croup who has been exposed to varicella would increase the risk of complicated varicella. Nonetheless, the American Academy of Pediatrics and the American Academy of Allergy and Immunology advise caution in using steroids in children with croup who have been exposed to varicella.2629 A child with moderate or severe croup should be treated with a steroidthe benefit of the steroid outweighs the riskbut a steroid for a child with milder disease and a history of recent varicella exposure merits cautious consideration.
Other theoretical complications of steroid treatment that require further study are bacterial tracheitis and gastrointestinal bleeding.9,19,21 Some authorities believe that bacterial tracheitis is related to unsuspected immune dysfunction. Gastrointestinal bleeding is highly unlikely in an otherwise healthy child, but may be a concern in one who has severe disease and requires care in the ICU, endotracheal intubation, and repeated high doses of a steroid.
As described in the vignette at the beginning of this article, your patient, Jack, has had symptoms of a "cold" for two days and spent most of the night awake, coughing. The cough has been distinctively "barking," his parents report, and you recognize it as croup. Jack looks generally well; has only a mild fever and no difficulty swallowing; and has experienced symptoms for only 24 hours.
On examination, you hear that distinctive cough and note that he has no stridor on inspiration and no chest wall indrawing. You decide that Jack's symptoms are mild and decide not to prescribe dexamethasone. You tell his parents how long they can expect the illness to last and, most important, when they should return for reassessment if his symptoms become worse, as they often do at night with croup.
The next day, you call Jack's home and learn that he had a much better night, with much less coughing.
If you determined that Jack has moderate or severe croup, treatment would be in order (Figure 3). He should receive a corticosteroid (dexamethasone, 0.6 mg/kg of body weight as a single oral dose) because the evidence of benefit is clear. Although all routes of administration are equally effective,10,29 we prefer oral dosing over the inhaled route, which is more time-consuming and expensive, and intramuscular administration, which is more painful. Treatment of moderate or severe croup with dexamethasone is effective and safe; additional clinical trials will determine whether steroids are also of benefit to children who have mild croup (we suspect that they are).
Before racemic epinephrine and steroids were introduced to treat croup, the disease caused significant morbidity. Some children were hospitalized, and some required intubation or tracheostomy for airway management. Deaths were also reported. But racemic epinephrine and steroids have drastically improved the outcome in children with severe croup, and have allowed many who would have once been admitted to the hospital to be safely and effectively managed as outpatients.
1. Skolnik N: Treatment of croup: A critical review. Am J Dis Child 1989;143:1045
2. Henrickson K, Kuhn S, Savatski L: Epidemiology and cost of infection with human parainfluenza virus types 1 and 2 in young children. Clin Infect Dis 1994;18:770
3. Marx A, Torok TJ, Holman RC, et al: Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. J Infect Dis 1997;176:1423
4. Denny FW, Murphy TF, Clyde WA Jr, et al: Croup: An 11-year study in a pediatric practice. Pediatrics 1983;71:871
5. Westley C, Cotton E, Brooks J: Nebulized racemic epinephrine by IPPB for the treatment of croup. Am J Dis Child 1978;132:484
6. Johnson DW, Jacobson S, Edney PC, et al: A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. N Engl J Med 1998;339:498
7. Klassen TP, Watters LK, Feldman ME, et al: The efficacy of nebulized budesonide in dexamethasone-treated outpatients with croup. Pediatrics 1996;97:463
8. Klassen TP, Feldman ME, Watters LK, et al: Nebulized budesonide for children with mild-to-moderate croup. N Engl J Med 1994;331:285
9. Johnson DW, Schuh S, Koren G, et al: Outpatient treatment of croup with nebulized dexamethasone. Arch Pediatr Adolesc Med 1996;150:349
10. Klassen TP, Craig WR, Moher D, et al: Nebulized budesonide and oral dexamethasone for treatment of croup: A randomized controlled trial. JAMA 1998;279:1629
11. 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
12. Geelhoed G, Macdonald W: Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg. Pediatr Pulmonol 1995;20:362
13. Orenstein D: Acute inflammatory upper airway obstruction, in Behrman R, Kliegman R, Jenson H (eds). Nelson's Textbook of Pediatrics, Toronto, Ont., WB Saunders, 2000, pp 12741279
14. Geelhoed G: Croup. Pediatr Pulmonol 1997;23:370
15. Henry R: Moist air in the treatment of laryngotracheitis. Arch Dis Child 1983;58:577
16. Bourchier D, Dawson K, Fergusson D: Humidification in viral croup: A controlled trial. Aust Paediatr J 1984;20:289
17. Wolfsdorf J, Swift D: An animal model simulating acute infective airway obstruction of childhood and its use in the investigation of croup therapy. Pediatr Res 1978;12:1062
18. Geelhoed G: Sixteen years of croup in a western Australian teaching hospital: Effects of routine steroid treatment. Ann Emerg Med 1996;28:621
19. Kairys S, Marsh-Olmstead E, O'Connor G: Steroid treatment of laryngotracheitis: A meta-analysis of the evidence from randomized trials. Pediatrics 1989;83:683
20. Ausejo M, Saenz A, Pham B, et al: The effectiveness of glucocorticoids in treating croup: Meta-analysis. Brit Med J 1999;319:595
21. King S: Canadian Paediatric Society statement: Steroid therapy for croup in children admitted to hospital. Can Med Assoc J 1992;147(4):429
22. Parainfluenza viral infections, in Peter G, Halsey NA, Marcuse EK, Packering LK, et al (eds): Red Book 1994. Report of the Committee on Infectious Diseases. Elk Grove Village, Ill., American Academy of Pediatrics, 1994, pp 341342
23. Geelhoed G, Turner J, Macdonald W: Efficacy of a small single dose of oral dexamethasone for outpatient croup: A double blind placebo controlled clinical trial. Brit Med J 1996;313:140
24. Dowell S, Bresee J: Severe varicella associated with steroid use. Pediatrics 1993;92:223
25. Patel H, Macarthur C, Johnson D: Recent corticosteroid use and the risk of complicated varicella in otherwise immunocompetent children. Arch Pediatr Adolesc Med 1996; 150:409
26. Draft position statement: Inhaled corticosteroids and severe viral infections. News and Notes. Milwaukee, Wisc., American Academy of Allergy and Immunology Committee on Drugs, 1992, p 3
27. Varicella-zoster infections, in Halsey N, Hall CB (eds): 1997 Red Book. Report of the Committee on Infectious Diseases. Elk Grove Village, Ill., American Academy of Pediatrics, 1997, p 702
28. New drug not routinely recommended for healthy children with chickenpox. Ottawa, Ontario: Canadian Pediatric Society, 1993
29. Rittichier K, Ledwith C: Outpatient treatment of moderate croup with dexamethasone: Intramuscular versus oral dosing. Pediatrics 2000;106:1344
The history and physical examination are your opportunity to exclude a number of differential diagnoses in the croup patient that can be serious or life-threatening.
Bacterial tracheitis is a life-threatening infection of the trachea that may be preceded by a recent history of croup. Most often, the child appears toxic and has a high fever. He (or she) has progressive respiratory distress, which typically does not improve with inhalation of racemic epinephrine. Soft-tissue radiographs of the neck may show an uneven or ragged-appearing tracheal wall. Visual inspection of the airway reveals purulent secretions exuding from below the vocal chords. Bacterial tracheitis requires quick recognition, intravenous antibiotic therapy, and admission to an ICU to treat potential acute obstruction by the thick, purulent respiratory secretions.1,2
Acute epiglottitis (supraglottitis) is a life-threatening bacterial infection of the epiglottis that has become rarer (but not unheard of) since a vaccine against Haemophilus influenzae type B was introduced. The patient most often exhibits a toxic appearance and high fever of sudden onset. He may refuse to speak or speaks in a very soft voice and may drool. He usually seems frightened and refuses to lie supine, preferring to sit up with the neck extended. A lateral neck radiograph shows an abnormally thickened epiglottis.
Acute epiglottitis is an airway emergency. The child must never be left unattended or transported out of an area without equipment and personnel for emergency airway management. The epiglottis must be visualized under controlled conditions by a staff member skilled in airway management, and intubation is almost always required to secure the airway.1,2
Retropharyngeal abscess is another cause of upper airway obstruction in young children. It results from bacterial infection of the lymph nodes that drain the head and neck to the retropharyngeal region. The infection results in expansion of what is normally a potential space, which then encroaches on the airway lumen. The diagnosis is confirmed by a lateral neck radiograph with the child positioned with the neck moderately extended. The film reveals widening of the prevertebral space. Treatment includes careful attention to the airway, IV antibiotics, and, in some cases, surgical drainage of the abscess.1,2
Asthma, a common chronic disease in children, is characterized by coughing, wheezing, and shortness of breath. Because cough is a principal symptom of asthma, it is possible to mistake the cough of asthma for croup.
Foreign body aspiration rarely presents with stridor, although it may be the presenting complaint with a high tracheal or esophageal foreign body. It is easy to miss the diagnosis initially because the child may not have the typical history of choking on an object. Radiographs may be helpful if the foreign body is radio-opaque, but films may also be completely normal. When a foreign body is suspected, therefore, rigid bronchoscopy is appropriate to identify and remove the foreign body.18,19
Airway compression (intraluminal or extraluminal) has a variety of causes, including airway hemangioma, hematoma caused by trauma, cyst, tumor, lymphadenopathy, and a foreign body in the esophagus. Although it is wise to include airway compression in the differential diagnosis of croup, the presentation is usually far more insidious, with symptoms that have gradually become evident or worse.
Allergic reaction and angioneurotic edema can present as acute airway obstruction. Anaphylaxis is a severe, systemic manifestation of type I hypersensitivity and usually occurs shortly after exposure to the offending antigen. The child often exhibits a combination of symptoms, including urticarial rash, respiratory distress caused by bronchospasm and airway edema, and cardiovascular collapse. Stridor may be a rare presenting symptom of anaphylaxis and should therefore be included in the differential diagnosis. Treatment entails the "ABCs," with subcutaneous epinephrine the initial drug of choice.
1. Orenstein D: Acute inflammatory upper airway obstruction, in Behrman R, Kliegman R, Jenson H (eds): Nelson's Textbook of Pediatrics, Toronto, Ont., WB Saunders, 2000, pp 12741279
2. Schweich P, Zempsky W: Selected topics in emergency medicine, in DeAngelis C, Feigin R, Warchaw J (eds): Oski's Pediatrics: Principles and Practice, Phildelphia, Pa., Lippincott Williams & Wilkins, 1999, pp 569576
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Date of publication: October 2001
Title: "That characteristic cough: When to treat croup and what to use"
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Candice Bjornson, David Johnson. CME: That characteristic cough: When to treat croup and what to use. Contemporary Pediatrics 2001;10:74.