All pediatricians should be familiar with the croup syndrome (laryngotracheobronchitis). The annual incidence among children in the United States is estimated to be 18 per I7OOO, with a peak incidence of 60 per 1,000 children 1 to 2 years old.1 In the 1970s and 1980s, considerable controversy existed over the role of systemic corticosteroids in the management of croup. Currently, their use is accepted with controversy mainly about the lowest effective dose and the method of delivery (intramuscular, oral, or nebulized). This article reviews the current treatment of and approach to laryngotracheobronchitis.
The acute croup syndrome typically has its onset in the middle of the night when the child awakens with some combination of a hoarse voice, barky cough, stridor, and respiratory distress. Children with classic viral croup often have a prodrome consisting of coryza and low-grade fever 12 to 72 hours prior to the onset of stridor. Patients with spasmodic croup have no prodrome or other warning signs prior to the dramatic onset of the classic symptoms. Although croup is often separated into spasmodic and viral forms, some argue that these distinctions are artificial and merely represent the ends of a spectrum of disease.2 Symptoms may persist for 3 to 7 days, but are most severe during the first 1 to 2 nights. The highest prevalence is in the second year of life, with a significant decrease in incidence after 6 years of age. Older children and adolescents may also have croup, but the diagnosis should alert the physician to consider other causes of upper airway obstruction. Boys are affected more often than girls. The peak seasons for croup are the fall and the winter.
The most common causes of laryngotracheobronchitis are the parainfluenza viruses, particularly types 1 and 2. Parainfluenza virus 1 is responsible for the biennial epidemics of croup seen in the fall months of odd years. Other common viral etiologies are influenza type A (often associated with severe disease), respiratory syncytial virus, adenovirus, and enterovirus.3 Measles virus can cause severe laryngotracheobronchitis, particularly in children younger than 2 years. Croup symptoms occur most often 2 days after the viral exanthem, but can occur before the skin eruption. Croup caused by measles virus is associated with a relatively high need for endotracheal intubation.4 Herpes simplex viruses have caused prolonged croup in both immunocompromised and immunocompetent hosts. Herpes simplex virus should be considered for patients with an unusually prolonged course, especially if associated with gingivostomatitis.5 Mycoplasme pneumoniae is a rare cause of croup. Historically, Corynebacterium diphtheriae was a major cause of croup and should still be considered in the unimmunized patient.
Although the diagnosis of croup is usually straightforward, several important entities need to be considered in the differential diagnosis of acute upper airway obstruction. Epiglottitis (supraglottitis) is an important consideration. However, it is rarely seen since the availability of vaccination against Haemophilus influenzae type B. Patients are typically older (usually 2 to 4 years old), with a rapid onset of high fever, muffled voice, dysphagia, drooling, and upper airway obstruction. The child is anxious, appears toxic, and tends to assume a sitting position with his or her chin pushed forward and neck hyperextended in an attempt to maintain an open airway.
Bacterial tracheitis most commonly presents as a superinfection following viral croup, but can manifest as a primary infection. This should be suspected when a child with croup shows initial improvement, then has a more toxic appearance, high fever, and increasing respiratory distress and becomes unresponsive to the usual treatments for viral croup. The diagnosis is usually made after bronchoscopy or intubation with recovery and culture of thick, purulent secretions. The most common organisms are Staphylococcus aureus, H. influenzae, Streptococcus pneumoniae, and, rarely, Moraxella catarrhalis. Other infectious considerations include retropharyngeal abscess, peritonsillar abscess, and uvulitis.
A variety of noninfectious etiologies need to be considered when evaluating the young child with acute upper airway obstruction, including foreign body, local trauma (ie, burns), angioneurotic edema (C1 esterase inhibitor deficiency), gastroesophageal reflux with laryngospasm, vocal cord paralysis in Arnold-Chiari malformation or ventriculoperitoneal shunt malfunction, hypocalcemia, and acute exacerbations of an underlying abnormality of the airway. Rapid onset of symptoms (eg, choking, stridor, or wheezing) during play or after earing should raise suspicion of a foreign body. Patients with angioneurotic edema usually have associated swelling of the face or the neck. Gastroesophageal reflux should be a consideration for patients with recurrent disease.6 Patients with Arnold-Chiari malformation and shunt dysfunction with acute stridor need rapid assessment of their vocal cord function. In these patients, acute brain stem herniation can cause bilateral paralysis of the vocal cords and acute stridor mimicking acute croup. Prompt surgical correction may save future vocal cord function and obviate the need for a tracheostomy. Symptoms of hypocalcemia include laryngospasm, muscle spasms, carpopedal spasm, and seizures. The QT interval on electroencephalogram is prolonged. A history of chronic stridor or prior intubation should lead one to suspect an underlying anatomic airway lesion exacerbated by a respiratory virus. Prompt referral to an airway specialist (pulmonologist or otolaryngologist) will aid in the diagnosis of the anatomic lesion and can, in some circumstances, be life saving. In an older child or adolescent, stridor that is prominent during the day but absent with sleep should raise the suspicion of psychogenic stridor (vocal cord dysfunction).
The diagnosis of croup should be made primarily on the basis of clinical findings. The radiologie findings of croup may include the tapered narrow subglottic airway in the anteroposterior view (steeple sign) or widening of the hypopharynx in the lateral view. These findings are present in only 50% of the cases of croup and do not correlate with disease severity. The specificity of these findings is also limited because some patients without croup may have a steeple sign as a normal variant.7,8 Because of their low sensitivity and specificity, radiographs are not useful in diagnosis but are more useful to evaluate for other possibilities in patients with atypical clinical findings.
Laryngotracheobronchitis is primarily a disease of the central (large) airway, so alveolar gas exchange is usually normal until a patient's condition is severe. The physician must remember not to be falsely reassured by a normal pulse oximetry reading and must carefully monitor the child with frequent examinations, paying particular attention to the degree of strider (with agitation only or at rest), retractions, and air entry.
Laryngoscopy is rarely needed to make the diagnosis of croup. It should be considered for cases with a history suggesting alternative diagnoses. These include patients with noisy respirations or an abnormal cry when well between episodes of croup; patients with a history of prior intubation; patients with progressively more severe or frequent episodes; patients who may have ingested a foreign body; and patients with symptoms severe enough to require intubation.
Most patients can be treated at home. Criteria for admission to the hospital include severe croup, the requirement for racemic epinephrine repeatedly, poor oral intake, unreliable caretakers, and living long distances from medical care.
Mist therapy began in the late 19th century when parents noted that steam from teakettles or hot tubs helped reduce the spasms of croup.2 Because of the risk of burns, cool mist has been used in hospital settings. For many years, this was administered by placing a child in a croup tent with humidified air, supplemented with oxygen if needed.
This practice has fallen out of favor in recent years. The only controlled trial investigating high humidity was unable to show any clinical benefits of humidification, although this study was performed on a small number of patients with relatively mild croup.9 Placing a child in a mist tent separates him or her from his or her parents and increases his or her anxiety, which can cause hyperventilation, increased airway obstruction, and increased work of breathing.10 Serial clinical examinations are made more difficult by trying to observe a child in a plastic tent sitting in a fog and may delay therapeutic intervention.
The "croup tent" no longer has a place in the treatment of a hospitalized patient. A trial of mist therapy may be given via a compressor-driven nebulizer and tubing while the child sits in the parent's comforting arms. If mist therapy is met with agitation, it should be stopped in favor of the more effective therapies outlined below. In the home setting, it is reasonable to give a trial of warm mist in the bathroom, which is most commonly achieved by running hot water in die shower or bath while sitting with the child.
In the first half of the 20th century, the main treatments were mist therapy and, for patients with severe airway obstruction not responsive to mist, tracheostomy or translaryngeal intubation.11 Racemic epinephrine, initially with intermittent positive pressure breathing and currently by simple nebulization, significantly reduced the need for an artificial airway. It is indicated for patients with respiratory distress. The beneficial effects are believed to be from the alpha-adrenergic effects causing vasoconstriction and decreased airway edema. The onset of action is 10 to 30 minutes with a maximal duration of action of approximately 2 hours.
Racemic epinephrine is composed of equal amounts of the D and the L isomers. It was used preferentially over L-epinephrine because it was believed that the racemic mixture caused fewer cardiovascular side effects. Most of the pharmacologie action is due to the L-isomer, which is 30 times more active than the D form. When similar amounts of the L isomer are given as either the racemic mixture or pure L-epinephrine, there is equal effectiveness without an increase in side effects.12 The doses used in die study were 0.5 mL of a 2.25% racemic epinephrine solution diluted in 4.5 mL of normal saline versus 5 mL of 1:1,000 L-epinephrine.
Early reports of a "rebound" worsening of respiratory distress 2 hours after administration led to the widespread recommendation that all children with croup treated with racemic epinephrine in the emergency department should be admitted to the hospital for observation regardless of posttreatment status. Rather than "rebound," the worsening or return of symptoms seen in some patients may reflect either the natural history of the disease process or the waning of the effect of a drug with a relatively short duration of action.
Several studies evaluated patients who received one dose of racemic epinephrine followed by a 2- to 4-hour observation period in the emergency department.13'15 All patients in these studies received systemic corticosteroids. The maximum benefit of racemic epinephrine was seen at 60 minutes. All patients who "relapsed" after initial improvement following the administration of racemic epinephrine did so within 3 hours.14 Patients observed for 3 hours were discharged home if they had croup scores of less than 2. Criteria for the croup score are listed in the table. Of the 61 patients sent home in the two prospective studies, only 1 patient returned to the emergency department for further medical attention.14'15 This patient returned 26 hours after initial discharge, received cool mist therapy, and was then discharged.
Croup Scoring System*
Patients with persistent strider or croup scores of greater than 2 within 3 hours of the racemic epinephrine dose should be admitted to the hospital. Patients who receive racemic epinephrine and systemic corticosteroids and have croup scores of less than 2 (free of intercostal retractions or stridor at rest) after a 3-hour observation period can be discharged safely, provided their parents can recognize the signs and symptoms of respiratory distress requiring them to return to the emergency department and they do not live too far from urgent medical care facilities. Kelley and Simon noted a potential cost savings of $1,115 per child sent home, assuming a hospital stay of 1 day.13
Considerable debate existed throughout the 1970s and early 1980s regarding the effectiveness of glucocorticoids in the treatment of croup. This debate ended in favor of glucocorticoids after a meta-analysis and subsequent data were published in 1989.(16,17) The most frequently studied glucocorticoids are dexamethasone given intramuscularly or orally and budesonide given by nebulization. The mechanism of action for the beneficial effects of corticosteroids in croup is not definitively known. Although the known antiinflammatory action may be important, the relatively rapid onset of action suggests vasoconstriction with reduced vascular permeability. This decreases subglottic edema and improves clinical symptoms.18
Historical comparisons in Australia show dramatic reductions in days in intensive care and intubations in a tertiary children's hospital since routine treatment with corticosteroids began. These changes were noted despite similar numbers of children being intubated in referral hospitals where corticosteroids were not used. This implies that the reduced morbidity at the tertiary hospital was due to the corticosteroids rather than to changes in the natural history of croup. Reductions in transfers to the intensive care unit within the hospital, length of stay, and admissions from the emergency department were also seen with routine corticosteroid use in the general hospital wards and the emergency department.19
Prospective, double-blind studies have shown similar findings. Geelhoed and Macdonald compared oral dexamethasone (0.6 mg/kg), nebulized budesonide (2 mg), and placebo in 80 children hospitalized with croup.20 The median duration of hospitalization was shorter in the two treatment groups. Rapid onset of action of corticosteroids was suggested by the lack of need for epinephrine treatments after the first hour compared with 20% of the children in the placebo group requiring epinephrine beyond 1 hour. No significant differences in these parameters were seen between the two treatment groups. Johnson et al. compared intramuscular dexamethasone (0.6 mg/kg), nebulized budesonide (4 mg), and placebo in 144 children with moderately severe croup in an emergency department setting and found reduced hospitalization rates in the treatment groups (23%, 38%, and 71%, respectively).21 Children who received intramuscular dexamethasone had significantly greater improvement in croup scores than did children who received budesonide. In another study, no advantage was seen to adding nebulized budesonide (2 mg) to oral dexamethasone.22
Route of Administration and Dosing
Oral dexamethasone appears to be as effective as intramuscular administration, although additional studies are needed.23 The dose of dexamethasone in most studies has been 0.6 mg/kg. Geelhoed and Macdonald performed a pair of sequential dosing studies in patients hospitalized with croup. They compared oral doses of 0.6 versus 0.3 mg/kg followed by 0.3 versus 0.15 mg/kg and noted similar efficacy in the reduction of croup scores, duration of hospitalization, and epinephrine use.24 Given the sequential design of the study and the relatively small number of patients, caution should be used before using the lower dosage, especially in light of the lack of adverse effects with the higher dosage.
Budesonide administered by nebulization is the preferred inhaled therapy. The dosage of budesonide most frequently used is 2 mg. This has shown the most success, whereas fluticasone propionate administered by metered dose inhaler did not demonstrate any benefit over placebo.25 However, only a small number of patients with relatively mild symptoms were studied, which may have made it more difficult to see statistically or clinically relevant changes.
Most of the studies cited above show similar outcomes for intramuscular, oral, or nebulized corticosteroids. The disadvantages of the nebulizer include the potential for increased agitation of the child and increased expense. Intramuscular doses obviously add to agitation and discomfort. Given its ease of administration and cost-effectiveness, the oral method of delivery is preferred, with intramuscular or nebulized corticosteroids reserved for patients unable or unwilling to tolerate the oral form.
During the past few decades, the treatment recommendations for croup have changed to reflect the safety and efficacy of corticosteroids. Oral corticosteroids are recommended for all patients with croup presenting to the emergency department or outpatient clinics with increased work of breathing. For patients who do not tolerate the oral preparation, nebulized or intramuscular corticosteroids are an excellent option. Racemic epinephrine or L-epinephrine should be used for patients with moderate or severe distress. A dose of epinephrine no longer necessitates hospital admission. Patients can be discharged safely if they receive corticosteroids and have no respiratory distress after 3 hours of observation.
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13. Kelley PB, Simon JE. Racemic epinephrine use in croup and disposition. Am } Emerg Med. 1992;10: 181-183.
14. Ledwith CA, Shea LM, Mauro RD. Safety and efficacy of nebulized racemic epinephrine in conjunction with oral dexamethasone and mist in the outpatient treatment of croup. Ann Emerg Med. 1995;25:331-337.
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17. Super DM, Cartelli NA, Brooks LJ, Lembo RM, Kumar ML. A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis. J Pediatr. 1989;115:323-329.
18. Klassen TP. Croup: a current perspective. Pediatr Clin North Am. 1999;46:1167-1178.
19. Geelhoed GC. Croup: state of the art. Pediatr Pulmonol. 1997;23:370-374.
20. Geelhoed GC, Macdonald WB. Oral and inhaled steroids in croup: a randomized, placebo-controlled trial. Pediatr Pulmonol. 1995;20:355-361.
21. Johnson DW, Jacobson S, Edney PC, Hadfield P, Mundy ME, Schuh S. A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. N Engl J Med. 1998;339:498-503.
22. Klassen TP, Craig WR, Moher D, et al. Nebulized budesonide and oral dexamethasone for treatment of croup. JAMA. 1998;279: 1629-1632.
23. Rittichier KK, Ledwith CA. Outpatient treatment of moderate croup with dexamethasone: intramuscular versus oral dosing. Pediatrics. 2000;106:1344-1348.
24. Geelhoed GC, Macdonald WB. Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg. Pediatr Pulmonol. 1995;20:362-368.
25. Roorda RJ, Walhof CM. Effects of inhaled fluticasone propionate administered with metered dose inhaler and spacer in mild to moderate croup: a negative preliminary report. Pediatr Pulmonol. 1998;25: 114-117.
Croup Scoring System*