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Croup: Pathogenesis and management
Tbekwrnalof
Emergency Medicine,Vol 1, pp. 3-l 1,1983
Printed in the USA
??
Copyright
0 1983 Pergamon
Press Ltd
Pediatrics CROUP: PATHOGENESIS AND MANAGEMENT Jeffrey L. Goldhagen,
MD
Director, Emergency Services, Minneapolis Children’s Health Center, 2525 Chicago Avenue, Minneapolis, MN 55404
examination. Evaluation and treatment must reflect the diagnostic considerations. Croup is a term that describes a complex of symptoms that result from varying degrees and locations of subglottic airway obstruction. As a manifestation of laryngeal, tracheal, or bronchial obstruction, it represents one of the common medical emergencies in pediatrics and must be approached with utmost sensitivity. Since croup is a symptom complex and not a pathologic diagnosis, the disease entities that produce acute obstruction must be specifically defined by the clinician so that rational and effective triage and treatment can be provided. An anatomical perspective is critical to relating the multiple etiologies, presentations, treatments, and prognoses to the structure, function, and pathology of the pediatric laryngotracheobronchial tree.
0 Abstract-Croup syndromes are common in children, most frequently being infectious in origin. Children present with a slow progression of inspiratory and expiratory stridor and a croupy, “barking seal” cough. Children are variably febrile and with progression of disease, exhaustion, agitation, cyanosis and air hunger may develop. The evaluation of the patient must focus on the degree of respiratory distress and associated findings. Epiglottitis and foreign body aspiration must be excluded. Management is primarily dependent upon administration of humidified air. Children with moderate to severe croup benefit from racemic epinephrine and steroids. Admission is indicated in children with stridor at rest, evidence of exhaustion, toxicity or respiratory distress. Active airway intervention is rarely required but may be life saving if obstruction develops. ? ?Keywords- croup; airway obstruction; subglottic obstruction
The unique characteristics of the pediatric airway, particularly the size and location of the larynx, establish a significant potential for obstruction with laryngeal edema. Croup syndromes are associated with a diffuse inflammatory response throughout the respiratory tree. Differential diagnosis must be based upon the peculiarities of the history, presentation and physical
Embryology, Pathology
Anatomy
and
The laryngotracheal tube, lined by endoderm, is the primordium of the entire respiratory system. By birth this endoderm has evolved into a mucus secreting membrane
Pediatrics spotlights two similar life-threatening medical emergencies - epiglottitis and croup. This section is coordinated by Roger Barkin, MD, ____ of the Department of Pediatrics at the University of Colorado. RECEIVED:14January 1983;ACCEPTED:23 February 1983 0736-4679/83$3.00+ .OO Clinical Communications:
=====
3
4
forming redundant folds in the region of the larynx. The entrance to the larynx is formed by the arytenoid swellings which begin as a T-shaped cleft, the margins of which are initially adherent and closed. In full-term infants the larynx has increased to an average diameter of 4 mm and is composed of 9 cartilages, the cricoid being the only continuous ring. The trachea is also a cartilaginous structure; however, the posterior portion of the tracheal rings is formed by the trachealis muscle. The average AP diameter of the infant trachea is 4.0 mm and the aperture of the larynx forms an isosceles triangle which measures 7x4mm.l If 1 mm of edema occurs in the region of the entrance to the larynx, the area will decrease from 13.9 to 8.7 mm2, a decrease of 35%. As the opening of the larynx occurs in the region of the cricoid cartilage, the effects of this edema are further multiplied. The combination of a complete cricoid ring that excludes outward expansion and the redundance of the laryngeal mucosa, increases the effects of even a small amount of edema. The infant’s airway is further compromised by other factors including: The absence of negative pleural distending pressure in the extrathoracic trachea; ?? The production of thick, viscid secretions by the mucus glands; ?? The dessication of these secretions due to an increased respiratory rate; and ?? The inability of the vocal cords to maximally abduct due to the presence of subglottic edema. ??
The embryologic evolution of the larynx from a closed to an open structure, and the common endodermal origin of the entire tracheobronchial tree may also contribute to the pathogenesis of subglottic obstruction. As the arytenoid swellings lose their continuity, varying orifice diameters may result in different obstructive potentials. Growth tends to negate the obstructive potential, but children under 12 months are especially at risk for significant airway compromise. The common origin, function, and con-
Jeffrey L. Goldhagen
tinuity of the entire laryngotracheobronchial tree results in diffuse dissemination of inflammation. Similar gross and histologic pathology are present in the larynx, trachea, and bronchi in children with infectious subglottic obstruction.233 Rabe’s description of these changes is most illustrative: The gross pathologic picture of so-called ‘virus’ croup was characterized by edema of the respiratory tract which was most marked in the subglottic region. The airway from the larynx to the bronchi contained a mucoid exudate and the lining epithelium was spottily covered by a fibrinous membrane. Microscopically, this membrane was composed of necrotic debris, fibrin, mucus, and a mixture of round cells and polynuclear leukocytes. Microscopic examination of the larynx, trachea, and bronchi showed a primary spotty surface ulceration with congestion and edema of the submucosa. The mucous glands showed variable degrees of toxic degeneration, from one area to another. In cases ill longest (e.g., 9 days) there was extensive glandular degeneration in all sections examined. In areas where such degeneration was severe, a fibrinous membrane was noted on the adjacent mucosa. In the lung the bronchiolar mucosa, and in some areas, the bronchiolar walls, were often destroyed and the lumina were plugged with polynuclear leukocytes and fibrin. A surrounding bronchopneumonia, atelectasis and alveolar emphysema were common. Microscopic evidence suggestive of pulmonary interstitial emphysema was usually found but in only one instance was this extensive.4 Recent studies have demonstrated longterm sequelae in children who have suffered
from even a single episode of a croup syndrome. Chronic pulmonary function abnormalities indicative of increased bronchial reactivity5 and residual small airway disease6 have been well documented. In children with croup, ventilation-perfusion abnormalities and not upper airway obstruction are the cause of hypoxia. Infiltrates on chest x-ray studies and the occasional finding of pulmonary edema, provide further evidence of generalized pathology.6 The pathogenesis of pulmonary edema is thought to result from the high negative in-
Croup: Pathogenesis
and Management
trathoracic pressures generated to overcome the obstruction in the upper airway. This results in alveolar and capillary damage,’ and a gradient large enough to pull an excess of fluid from the alveolar capillaries. Hypoxia and a catecholamine mediated shift of blood from the systemic to the pulmonary circulation may further contribute to the edema.*
Etiologic Considerations There are multiple agents associated with the broad spectrum of croup syndromes. Infectious croup was first described in chickens by May and Tittsler in 1925.9 They were able to demonstrate its transmission by ultrafiltrates suggesting a viral etiology. Brighton’s review of laryngotracheobronchitis (LTB) in 1940 was the first to suggest a viral etiology in humans.rO He found mononuclear cell infiltration in human tracheal sections similar to that previously noted in chickens. Rabe in a series of three articles in 1948,4~11~12 further differentiated viral from bacterial croup by its presentation and pathophysiology. The majority of infectious croup is caused by viruses. Parainfluenza 1,2, and 3 are the most common viral agents, followed by respiratory syncytial virus (RSV), adenoviruses, influenza and measles, depending on the season and epidemiologic patterns in the community. Specific agents tend to cause differing degrees of respiratory distress and obstruction. Influenza A, virus is particularly virulent. I3 Over the last several decades, the bacterial etiology of croup syndrome has been largely ignored until a report by Jones et al in 1979 described 8 children with the “new” entity of bacterial tracheitis.14 This was followed by other reports, most of which document Staphylococcus aureus as the primary etiologic agent. 15,16 Bacteria may be secondary invaders following viral induced susceptibility of the respiratory tract. Foreign body aspiration may also result in croup. Most frequently the object will
5
be a peanut or other food matter and therefore radiolucent. Since the diameter of the trachea is relatively constant beyond the larynx, foreign bodies that clear the larynx, commonly lodge at the carina or mainstem bronchi. Foreign bodies may also lodge in the esophagus (particularly coins and bones) and result in croup secondary to extrinsic laryngotracheal compression. Other noninfectious causes of “croup” include spasmodic or allergic croup due to exposure to an irritating or sensitizing agent, neoplasms and compression secondary to anomalies of the great vessels.
Presentation, Physical Exam and History Infectious croup may present acutely, but is usually preceded by an upper respiratory tract infection followed by the gradual onset of a croup symptom complex. Symptoms include inspiratory stridor, a prolonged expiratory component of respiration often accompanied by wheezing, hoarseness, retractions, rapid and labored respirations, tachycardia and the classic, croupy, “barking seal” cough. With severe or prolonged disease, the child may present with exhaustion, agitation, air hunger, cyanosis, or an ashen gray appearance. The children are variably febrile, rarely reaching 103- 105“F and are usually able to lie on their back, manage oral secretions and are seldom cyanotic or in acute respiratory distress. The epiglottis is not distinctly enlarged or edematous although erythema of the pharyngotonsillar area may be present. Auscultation may reveal rales, rhonchi, localized areas of decreased breath sounds and a shift of heart sounds. Of utmost importance in the evaluation of the child is the pattern of progression. Diminution in stridor and retractions may indicate impending cardiorespiratory collapse. The child with epiglottitis will usually be more toxic in appearance than the infant with croup. He/she has difficulty handling oral secretions, is unable to lie backward,
Jeffrey L. Goldhagen
6
sits with the neck extended and the jaw thrust forward to maximize the laryngeal aperture, may complain of tenderness to palpation of the neck and has a history of the sudden onset of symptoms. As this is a disease of supraglottic structures, croup symptoms are not present (Table 1).
Ancillary Evaluations There are two components to the diagnostic evaluation. The clinician must first define the disease process and then the extent of involvement must be delineated. The clinical presentation and lateral neck and AP chest x-ray studies help differentiate between supraglottic (epiglottitis) and subglottic obstruction. Patients should never be sent to x-ray unless accompanied by an experienced clinician, skilled in airway management. Portable x-rays may be helpful. In croup, the obstruction of the larynx and trachea results in overaeration and distention of the airway proximal to the site of obstruction during inspiration, and varying degrees of aeration of the lungs.” The
PA chest x-ray study in a child with croup will therefore reveal distention of the hypopharynx and a high, domed diaphragm. The film will also reveal a long segment of tracheal narrowing on inspiration (the socalled steeple sign) and blurring of the tracheal air shadow (Figure 1). A short segment of tracheal narrowing at its origin is normal. Expiratory films will tend to negate the abnormal x-ray findings of subglottic obstruction. In epiglottitis there is usually marked enlargement of the epiglottis on soft-tissue lateral neck x-ray study (Figures 2 and 3). However, a child can present with lifethreatening supraglottic obstruction with a normal epiglottis on x-ray exam, the infection being limited to the aryepiglottic folds. If a foreign body is present, inspiratory-expiratory AP chest films and lateral decubitus chest x-ray studies may reveal a shift of the mediastinum and emphysematous changes in the lungs. More often, however, fluoroscopy will be required, especially if the object is radiolucent, There is no correlation between roentgenographic findings and the severity of the disease process.18Jg
Table 1. Comparison 01 Croup and Epiglottitis Diagnostic Findings
Me
Seasonal occurrence Worst time of day Etiology Clinical signs/symptoms Onset Fever Toxic Sore throat Voice Drooling Cough Preferred position Stridor Epiglottis Ancillary data WBC Blood culture ABG X-ray, lat neck
Croup
Epiglottitis
6 mo-3 yr Fall/winter Night/early am Viral
Any age (peak: 2-5 yr) None Throughout day H. influenzae
Insidious <103”F No Variable Hoarse No “Barking seal” Variable lnspirlexpir Normal
Rapid High Yes Yes Muffled Yes None Prefers sitting lnspir “Cherry red”
Normal Negative Variable Normal
High Positive Variable Enlarged epiglottis
Source: Barkin RM, Rosen P: Emergency
Pediatrics.
St. Louis,
CV Mosby, in press.
Croup: Pathogenesis and Management
7
Figure 1. Anterior-posterior x-ray of the larynx and trachea of a child with croup. Note the presence of the “steeple sign.”
Figure 2. Soft tissue lateral neck x-ray of a child with epiglottitis.
Jeffrey L. Goldhagen
8
Figure 3. Soft tissue lateral neck x-ray of a normal child.
Other objective tools for assessment include arterial blood gas measurements and the assessment of clinical parameters. The clinical appraisal of alveolar hypoventilation is not accurate; serial blood gas measurements are indicated with severe disease. Hypoxemia is frequently present and an earlier indicator of respiratory compromise than changes in Pco,; however, a rise in Pco, is a more sensitive indicator of the severity of pulmonary disease. Absence of cyanosis does not preclude hypoxemia. Respiratory and heart rates, although not sensitive, are nevertheless the best clinical indicators of hypoxemia. Neither, however, correlate well with hypercapnea.m Air entry and degree of stridor are difficult to objectively and reliably assess. The natural history of croup is difficult to predict; therefore all available tools must be utilized to determine the status of the individual child. The Clinical Croup Score developed by Downes and Raphaely*r (Table 2) provides an objective clinical assessment. An additive score of 4 or more
indicates moderately severe upper airway obstruction that may benefit from therapeutic intervention. A score of 7 or more, particularly when associated with a Pace, 2 45 torr and a Pao,< 70 torr (sea level, room air) that persists despite therapeutic intervention, may indicate the need for active airway management.
Management A rational plan of management for the child with subglottic obstruction must consider the anatomy, etiologic agents, differential diagnoses, clinical presentations and the limitations of clinical and laboratory diagnostic tools. Often the initial encounter is a telephone consultation. The Clinical Croup Score*’ may be helpful in determining the severity of the disease although stridor at rest or any evidence of respiratory distress necessitates immediate evaluation and intervention. One must try to identify the infant
Croup: Pathogenesis
9
and Management
who is approaching exhaustion from whatever cause of obstruction. Also important is to identify the child who has the sudden onset of fever, toxicity, drooling and the inability to lie on his/her back. These children need immediate medical care. Potential foreign body ingestion as well as allergen exposure (spasmodic croup) must be excluded. Children with a history of prematurity, neonatal pulmonary disease, or intubation are at greater risk for airway obstruction from any cause of croup. Upon presentation, management must take precedence over evaluation. The epiglottis and pharyngotonsillar tissues must be visualized after preoxygenating the child in a careful and deliberate fashion. Visualization should only be performed, however, if the clinician is prepared to intubate the child should acute obstruction occur. There is usually little need for a soft-tissue lateral neck film. The child with epiglottitis or supraglottitis should be intubated in a controlled manner as outlined by Grodin.22. If there is no evidence of acute epiglottitis or a foreign body, the patient’s respiratory status must dictate the extent of further evaluation and treatment. The majority of patients present with a history of mild upper respiratory tract infection and gradual onset of croup. If the Clinical Croup Score21 is less than 4, the child does not appear toxic, there is no respiratory distress and the child does not have stridor at rest, no x-ray or laboratory studies are indicated and the patient may
be discharged home after arrangements are made for mist therapy and the importance of pushing fluids is emphasized. Parents should be encouraged to call or return if there is any question of deterioration, particularly with increasing respiratory distress, cyanosis, drooling, agitation or stridor. Obviously, this approach must be modified if there are communication, compliance, or transportation problems. If the child has stridor at rest, evidence of exhaustion, toxicity, or respiratory distress, admission should be facilitated. The hallmark of management remains mist therapy with close and ongoing observation. Racemic epinephrine (Micronephrine 2%) has been clearly demonstrated to be beneficial.22-2a The solution is mixed so that 0.5 mL is placed in a nebulizer with 2.5 mL of normal saline and administered with or without IPPB over 8 to 15 min. Improvement of symptoms should be rapidly noted with a duration of action of 1 to 2 hours. The treatments may be repeated as needed but are contraindicated in children with cardiac outlet obstructions. Because of the consistent rebound in symptoms, all patients requiring racemic epinephrine should be admitted.23-29 Steroids remain controversial but have been used by many clinicians with impressive success in children with croup symptoms. Dexamethasone 0.30 to 0.50 mg/kg/dose is given parenterally every 6 hours.30~3r~32 It is generally indicated in children requiring racemic epinephrine. Fluid intake should be encouraged.
Table 2. Clinical Croup Score Score Clinical Parameter
0
lnspiratory breath sounds Stridor Cough Retractions and flaring
Normal None None None
Cyanosis
None
Source:
Downes J, Raphaely
R: Pediatric
intensive
1 Harsh with rhonchi lnspiratory Hoarse cry Flaring and supersternal retractions In air care. Anesthesiology
2 Delayed lnspiratory and expiratory Bark As under 1 plus subcostal, intercostal retractions In 40% 0, 1975; 43:242
Jeffrey L. Goldhagen
10
Patients with spasmodic or allergic croup respond dramatically to racemic epinephrine with total resolution of signs and symptoms. However, such patients should be admitted after their initial treatment because of the potential for rebound of symptoms post treatment. If a child with croup presents with a definite history of aspiration of a foreign body, bronchoscopy should be arranged and fluoroscopy performed, assuming that no acute upper airway obstruction exists. If the history is equivocal, fluoroscopy should be initially performed. A positive study will reveal asymmetric movement of the diaphragm on inspiration. Inspiratoryexpiratory PA chest x-ray studies and right and left lateral decubitus chest x-ray studies looking for asymmetric air trapping and shifts of the mediastinum are not usually reliable enough to use as the sole diagnostic tools. Physical examination may reveal wheezing or distinct asymmetry of breath sounds. The history of a prolonged course of croup or the gradual onset of symptoms are both consistent with the diagnosis of foreign body aspiration. If the patient is not responding or has an unusual course, direct laryngoscopy (or bronchoscopy) should be considered to evaluate for bacterial subglottitis (tracheitis), most commonly caused by Staphylococcus aureus. There are no roentgenograph or laboratory investigations that will differentiate bacterial from viral subglottitis. 15If mucosal edema and copious purulent material are noted, the child should be cultured, methicillin (or equivalent) 100
mg/kg/24 h every 4 hours intravenously begun and intubation considered. If improvement of croup symptoms in the child with viral disease is not forthcoming after initiating routine measures, active airway management may be necessary. Only 2-5% of hospitalized children with subglottic obstruction will require airway management, the preferred procedure being nasotracheal intubation. Downes’ score may be used21 to help determine the severity of respiratory distress (Table 2). Oxygen without intubation is rarely indicated since hypoxia serves as one indicator for assessing airway patency and ventilation/perfusion abnormalities limit improvement with oxygen administration. The child should also be evaluated for pulmonary edema and cardiac failure.
Summary
Airway obstruction represents a true medical emergency. The child with croup has some degree of airway obstruction and must be individually and carefully assessed. Special considerations must be given to the infant’s relatively small airway and the generalized nature of the abnormal pathology. Diagnosis, treatment and triage of the patient with subglottic airway obstruction may then be appropriately initiated. Acknowledgement-X-rays
courtesy of Shashikant Sane, MD, Minneapolis Medical Center, and William Cranley, MD, Boston City Hospital.
REFERENCES 1. Holinger P, Johnston K: Factors responsible for laryngeal obstruction in infants. JAM4 1950: _ 143:1229. 2. Orton H, Smith L, Bell H, Ford R: Acute laryngotracheobronchitis. Arch Otolaryng 1941; 33: 926. 3. Brennemann J, Clifton W, Frank A, Holinger P: Acute laryngotracheobronchitis. Amer J Dis Child 1938; 55:667. 4. Rabe E: Infectious croup, II. Virus. Pediatrics 1948; 2:415.
5. Loughlin Cl, Taussig L: Pulmonary function in children with a history of laryngotracheobronchitis. J Pediat 1979; 94:365. 6. Taussig L: Clinical and physiologic evidence for the persistence of pulmonary abnormalities after respiratory illnesses in infancy and childhood. Pediatr Res 1977; 11:216. 7. Oswalt C, Gates G, Holstrom F: Pulmonary edema as a complication of acute airway obstruction. JAM4 1977; 238:1833. 8. Travis K, Todres I, Shannon D: Pulmonary ede-
Croup: Pathogenesis
and Management
ma associated with croup and epiglottitis. Pediatrics 1977; 59695. 9. May H, Tittsler R: Laryngotracheitis in chickens. J Amer Vet Med Asso 1925; 67~229. 10. Brighton G: Laryngotracheobronchitis. Ann Otorhinolatyng 1940; 49: 1070. 11. Rabe E: Infectious croup, I, Etiology. Pediatrics 1948; 2:255. 12. Rabe E: Infectious croup, III, Hemophilus influenzae type B croup. Pediatrics 1948; 2:559. 13. Howard J, McCracken G, Luby J: Influenza A2 virus as a cause of croup requiring tracheotomy. J Pediatr 1972; 81:1148. 14. Jones R, Santos J, Overall J: Bacterial tracheitis. JAMA 1979; 242:721. 15. Liston S, Gehrz R, Jarvis C: Bacterial tracheitis. Arch Otolaryng 1981; 107:561. 16. Helfinaer D: Croun vs. enialottitis vs. tracheitis. JAMA-1981; 246:iO87. - 17. Capitanio M, Kirkpatrick J: Obstructions of the upper airway in children as reflected on the chest radiograph. Radiology 1973; 107:159. 18. Mills J, Spackman T, Borns P, Mandell G, Schwartz W: The usefulness of lateral neck roentgenograms in LTB. Amer J Dis Child 1979; 133: 1140. 19. DeLevie M, Nogrady M, Spence L: Acute LTB (croup): Correlation of clinical severity with radiologic and virologic findings. Ann Radiot 1971; 15:193. 20. Newth C, Levison H, Bryan A: The respiratory status of children with crouu. J Pediatr 1972: 82: 1068. 21. Downes J, Raphaely R: Pediatric intensive care. Anesthesiology 1975; 43:242.
11
22. Grodin M: Epiglottitis. J Emerg Med 1983; 1: 13. 23. Corkey C, Barker G, Edmonds M, Mok P, Newth C: Radiographic tracheal diameter measurements in acute infectious croup: An objective scoring system. Crit CareMed 1981; 9:587. 24. Lenney W, Mimer A: Treatment of acute viral croup. Arch Dis Child 1978; 53:704. 25. Westley C, Cotton E, Brooks J: Nebulized racemic epinephrine by IPPB for the treatment of croup. Amer JDk Child 1978; 132:484. 26. Singer 0, Wilson W: Laryngotracheobronchitis: Two years’ experience with racemic epinephrine. CanadMAssn J 1976; 115:132. 27. Taussig L, Castro 0, Beaudry P, Fox W, Burean M: Treatment of LTB (croup), use of intermittent positive-pressure breathing and racemic epinephrine. Amer J DtLsChild 1975; 129:79. 28. Gardner G, Powell K, Raden V, Cherry J: The evaluation of racemic epinephrine in the treatment of infectious croup. Pediatrics 1973; 52:52. 29. Adair J, Ring W, Jordan W, Elwyn R: Ten year experience with IPPB in the treatment of acute LTB. Anesth Ann 1971; 50649. 30. Hawkins D: Corticosteroids in the management Otolaryng Head of laryngotracheobronchitis. Neck Surg 1980; 88:207. 31. Tunnessen W, Feinstein A: The steroid-croup controversy: An analytic review of methodologic problems. J Pediafr 1980; 96:751. 32. Leipzig B, Oski F, Cummings C, Stockman J, Swender P: A prospective randomized study to determine the efficacy of steroids in treatment of croup. J Pediatr 1979; 94: 194.
Emergency Medicine,Vol 1, pp. 3-l 1,1983
Printed in the USA
??
Copyright
0 1983 Pergamon
Press Ltd
Pediatrics CROUP: PATHOGENESIS AND MANAGEMENT Jeffrey L. Goldhagen,
MD
Director, Emergency Services, Minneapolis Children’s Health Center, 2525 Chicago Avenue, Minneapolis, MN 55404
examination. Evaluation and treatment must reflect the diagnostic considerations. Croup is a term that describes a complex of symptoms that result from varying degrees and locations of subglottic airway obstruction. As a manifestation of laryngeal, tracheal, or bronchial obstruction, it represents one of the common medical emergencies in pediatrics and must be approached with utmost sensitivity. Since croup is a symptom complex and not a pathologic diagnosis, the disease entities that produce acute obstruction must be specifically defined by the clinician so that rational and effective triage and treatment can be provided. An anatomical perspective is critical to relating the multiple etiologies, presentations, treatments, and prognoses to the structure, function, and pathology of the pediatric laryngotracheobronchial tree.
0 Abstract-Croup syndromes are common in children, most frequently being infectious in origin. Children present with a slow progression of inspiratory and expiratory stridor and a croupy, “barking seal” cough. Children are variably febrile and with progression of disease, exhaustion, agitation, cyanosis and air hunger may develop. The evaluation of the patient must focus on the degree of respiratory distress and associated findings. Epiglottitis and foreign body aspiration must be excluded. Management is primarily dependent upon administration of humidified air. Children with moderate to severe croup benefit from racemic epinephrine and steroids. Admission is indicated in children with stridor at rest, evidence of exhaustion, toxicity or respiratory distress. Active airway intervention is rarely required but may be life saving if obstruction develops. ? ?Keywords- croup; airway obstruction; subglottic obstruction
The unique characteristics of the pediatric airway, particularly the size and location of the larynx, establish a significant potential for obstruction with laryngeal edema. Croup syndromes are associated with a diffuse inflammatory response throughout the respiratory tree. Differential diagnosis must be based upon the peculiarities of the history, presentation and physical
Embryology, Pathology
Anatomy
and
The laryngotracheal tube, lined by endoderm, is the primordium of the entire respiratory system. By birth this endoderm has evolved into a mucus secreting membrane
Pediatrics spotlights two similar life-threatening medical emergencies - epiglottitis and croup. This section is coordinated by Roger Barkin, MD, ____ of the Department of Pediatrics at the University of Colorado. RECEIVED:14January 1983;ACCEPTED:23 February 1983 0736-4679/83$3.00+ .OO Clinical Communications:
=====
3
4
forming redundant folds in the region of the larynx. The entrance to the larynx is formed by the arytenoid swellings which begin as a T-shaped cleft, the margins of which are initially adherent and closed. In full-term infants the larynx has increased to an average diameter of 4 mm and is composed of 9 cartilages, the cricoid being the only continuous ring. The trachea is also a cartilaginous structure; however, the posterior portion of the tracheal rings is formed by the trachealis muscle. The average AP diameter of the infant trachea is 4.0 mm and the aperture of the larynx forms an isosceles triangle which measures 7x4mm.l If 1 mm of edema occurs in the region of the entrance to the larynx, the area will decrease from 13.9 to 8.7 mm2, a decrease of 35%. As the opening of the larynx occurs in the region of the cricoid cartilage, the effects of this edema are further multiplied. The combination of a complete cricoid ring that excludes outward expansion and the redundance of the laryngeal mucosa, increases the effects of even a small amount of edema. The infant’s airway is further compromised by other factors including: The absence of negative pleural distending pressure in the extrathoracic trachea; ?? The production of thick, viscid secretions by the mucus glands; ?? The dessication of these secretions due to an increased respiratory rate; and ?? The inability of the vocal cords to maximally abduct due to the presence of subglottic edema. ??
The embryologic evolution of the larynx from a closed to an open structure, and the common endodermal origin of the entire tracheobronchial tree may also contribute to the pathogenesis of subglottic obstruction. As the arytenoid swellings lose their continuity, varying orifice diameters may result in different obstructive potentials. Growth tends to negate the obstructive potential, but children under 12 months are especially at risk for significant airway compromise. The common origin, function, and con-
Jeffrey L. Goldhagen
tinuity of the entire laryngotracheobronchial tree results in diffuse dissemination of inflammation. Similar gross and histologic pathology are present in the larynx, trachea, and bronchi in children with infectious subglottic obstruction.233 Rabe’s description of these changes is most illustrative: The gross pathologic picture of so-called ‘virus’ croup was characterized by edema of the respiratory tract which was most marked in the subglottic region. The airway from the larynx to the bronchi contained a mucoid exudate and the lining epithelium was spottily covered by a fibrinous membrane. Microscopically, this membrane was composed of necrotic debris, fibrin, mucus, and a mixture of round cells and polynuclear leukocytes. Microscopic examination of the larynx, trachea, and bronchi showed a primary spotty surface ulceration with congestion and edema of the submucosa. The mucous glands showed variable degrees of toxic degeneration, from one area to another. In cases ill longest (e.g., 9 days) there was extensive glandular degeneration in all sections examined. In areas where such degeneration was severe, a fibrinous membrane was noted on the adjacent mucosa. In the lung the bronchiolar mucosa, and in some areas, the bronchiolar walls, were often destroyed and the lumina were plugged with polynuclear leukocytes and fibrin. A surrounding bronchopneumonia, atelectasis and alveolar emphysema were common. Microscopic evidence suggestive of pulmonary interstitial emphysema was usually found but in only one instance was this extensive.4 Recent studies have demonstrated longterm sequelae in children who have suffered
from even a single episode of a croup syndrome. Chronic pulmonary function abnormalities indicative of increased bronchial reactivity5 and residual small airway disease6 have been well documented. In children with croup, ventilation-perfusion abnormalities and not upper airway obstruction are the cause of hypoxia. Infiltrates on chest x-ray studies and the occasional finding of pulmonary edema, provide further evidence of generalized pathology.6 The pathogenesis of pulmonary edema is thought to result from the high negative in-
Croup: Pathogenesis
and Management
trathoracic pressures generated to overcome the obstruction in the upper airway. This results in alveolar and capillary damage,’ and a gradient large enough to pull an excess of fluid from the alveolar capillaries. Hypoxia and a catecholamine mediated shift of blood from the systemic to the pulmonary circulation may further contribute to the edema.*
Etiologic Considerations There are multiple agents associated with the broad spectrum of croup syndromes. Infectious croup was first described in chickens by May and Tittsler in 1925.9 They were able to demonstrate its transmission by ultrafiltrates suggesting a viral etiology. Brighton’s review of laryngotracheobronchitis (LTB) in 1940 was the first to suggest a viral etiology in humans.rO He found mononuclear cell infiltration in human tracheal sections similar to that previously noted in chickens. Rabe in a series of three articles in 1948,4~11~12 further differentiated viral from bacterial croup by its presentation and pathophysiology. The majority of infectious croup is caused by viruses. Parainfluenza 1,2, and 3 are the most common viral agents, followed by respiratory syncytial virus (RSV), adenoviruses, influenza and measles, depending on the season and epidemiologic patterns in the community. Specific agents tend to cause differing degrees of respiratory distress and obstruction. Influenza A, virus is particularly virulent. I3 Over the last several decades, the bacterial etiology of croup syndrome has been largely ignored until a report by Jones et al in 1979 described 8 children with the “new” entity of bacterial tracheitis.14 This was followed by other reports, most of which document Staphylococcus aureus as the primary etiologic agent. 15,16 Bacteria may be secondary invaders following viral induced susceptibility of the respiratory tract. Foreign body aspiration may also result in croup. Most frequently the object will
5
be a peanut or other food matter and therefore radiolucent. Since the diameter of the trachea is relatively constant beyond the larynx, foreign bodies that clear the larynx, commonly lodge at the carina or mainstem bronchi. Foreign bodies may also lodge in the esophagus (particularly coins and bones) and result in croup secondary to extrinsic laryngotracheal compression. Other noninfectious causes of “croup” include spasmodic or allergic croup due to exposure to an irritating or sensitizing agent, neoplasms and compression secondary to anomalies of the great vessels.
Presentation, Physical Exam and History Infectious croup may present acutely, but is usually preceded by an upper respiratory tract infection followed by the gradual onset of a croup symptom complex. Symptoms include inspiratory stridor, a prolonged expiratory component of respiration often accompanied by wheezing, hoarseness, retractions, rapid and labored respirations, tachycardia and the classic, croupy, “barking seal” cough. With severe or prolonged disease, the child may present with exhaustion, agitation, air hunger, cyanosis, or an ashen gray appearance. The children are variably febrile, rarely reaching 103- 105“F and are usually able to lie on their back, manage oral secretions and are seldom cyanotic or in acute respiratory distress. The epiglottis is not distinctly enlarged or edematous although erythema of the pharyngotonsillar area may be present. Auscultation may reveal rales, rhonchi, localized areas of decreased breath sounds and a shift of heart sounds. Of utmost importance in the evaluation of the child is the pattern of progression. Diminution in stridor and retractions may indicate impending cardiorespiratory collapse. The child with epiglottitis will usually be more toxic in appearance than the infant with croup. He/she has difficulty handling oral secretions, is unable to lie backward,
Jeffrey L. Goldhagen
6
sits with the neck extended and the jaw thrust forward to maximize the laryngeal aperture, may complain of tenderness to palpation of the neck and has a history of the sudden onset of symptoms. As this is a disease of supraglottic structures, croup symptoms are not present (Table 1).
Ancillary Evaluations There are two components to the diagnostic evaluation. The clinician must first define the disease process and then the extent of involvement must be delineated. The clinical presentation and lateral neck and AP chest x-ray studies help differentiate between supraglottic (epiglottitis) and subglottic obstruction. Patients should never be sent to x-ray unless accompanied by an experienced clinician, skilled in airway management. Portable x-rays may be helpful. In croup, the obstruction of the larynx and trachea results in overaeration and distention of the airway proximal to the site of obstruction during inspiration, and varying degrees of aeration of the lungs.” The
PA chest x-ray study in a child with croup will therefore reveal distention of the hypopharynx and a high, domed diaphragm. The film will also reveal a long segment of tracheal narrowing on inspiration (the socalled steeple sign) and blurring of the tracheal air shadow (Figure 1). A short segment of tracheal narrowing at its origin is normal. Expiratory films will tend to negate the abnormal x-ray findings of subglottic obstruction. In epiglottitis there is usually marked enlargement of the epiglottis on soft-tissue lateral neck x-ray study (Figures 2 and 3). However, a child can present with lifethreatening supraglottic obstruction with a normal epiglottis on x-ray exam, the infection being limited to the aryepiglottic folds. If a foreign body is present, inspiratory-expiratory AP chest films and lateral decubitus chest x-ray studies may reveal a shift of the mediastinum and emphysematous changes in the lungs. More often, however, fluoroscopy will be required, especially if the object is radiolucent, There is no correlation between roentgenographic findings and the severity of the disease process.18Jg
Table 1. Comparison 01 Croup and Epiglottitis Diagnostic Findings
Me
Seasonal occurrence Worst time of day Etiology Clinical signs/symptoms Onset Fever Toxic Sore throat Voice Drooling Cough Preferred position Stridor Epiglottis Ancillary data WBC Blood culture ABG X-ray, lat neck
Croup
Epiglottitis
6 mo-3 yr Fall/winter Night/early am Viral
Any age (peak: 2-5 yr) None Throughout day H. influenzae
Insidious <103”F No Variable Hoarse No “Barking seal” Variable lnspirlexpir Normal
Rapid High Yes Yes Muffled Yes None Prefers sitting lnspir “Cherry red”
Normal Negative Variable Normal
High Positive Variable Enlarged epiglottis
Source: Barkin RM, Rosen P: Emergency
Pediatrics.
St. Louis,
CV Mosby, in press.
Croup: Pathogenesis and Management
7
Figure 1. Anterior-posterior x-ray of the larynx and trachea of a child with croup. Note the presence of the “steeple sign.”
Figure 2. Soft tissue lateral neck x-ray of a child with epiglottitis.
Jeffrey L. Goldhagen
8
Figure 3. Soft tissue lateral neck x-ray of a normal child.
Other objective tools for assessment include arterial blood gas measurements and the assessment of clinical parameters. The clinical appraisal of alveolar hypoventilation is not accurate; serial blood gas measurements are indicated with severe disease. Hypoxemia is frequently present and an earlier indicator of respiratory compromise than changes in Pco,; however, a rise in Pco, is a more sensitive indicator of the severity of pulmonary disease. Absence of cyanosis does not preclude hypoxemia. Respiratory and heart rates, although not sensitive, are nevertheless the best clinical indicators of hypoxemia. Neither, however, correlate well with hypercapnea.m Air entry and degree of stridor are difficult to objectively and reliably assess. The natural history of croup is difficult to predict; therefore all available tools must be utilized to determine the status of the individual child. The Clinical Croup Score developed by Downes and Raphaely*r (Table 2) provides an objective clinical assessment. An additive score of 4 or more
indicates moderately severe upper airway obstruction that may benefit from therapeutic intervention. A score of 7 or more, particularly when associated with a Pace, 2 45 torr and a Pao,< 70 torr (sea level, room air) that persists despite therapeutic intervention, may indicate the need for active airway management.
Management A rational plan of management for the child with subglottic obstruction must consider the anatomy, etiologic agents, differential diagnoses, clinical presentations and the limitations of clinical and laboratory diagnostic tools. Often the initial encounter is a telephone consultation. The Clinical Croup Score*’ may be helpful in determining the severity of the disease although stridor at rest or any evidence of respiratory distress necessitates immediate evaluation and intervention. One must try to identify the infant
Croup: Pathogenesis
9
and Management
who is approaching exhaustion from whatever cause of obstruction. Also important is to identify the child who has the sudden onset of fever, toxicity, drooling and the inability to lie on his/her back. These children need immediate medical care. Potential foreign body ingestion as well as allergen exposure (spasmodic croup) must be excluded. Children with a history of prematurity, neonatal pulmonary disease, or intubation are at greater risk for airway obstruction from any cause of croup. Upon presentation, management must take precedence over evaluation. The epiglottis and pharyngotonsillar tissues must be visualized after preoxygenating the child in a careful and deliberate fashion. Visualization should only be performed, however, if the clinician is prepared to intubate the child should acute obstruction occur. There is usually little need for a soft-tissue lateral neck film. The child with epiglottitis or supraglottitis should be intubated in a controlled manner as outlined by Grodin.22. If there is no evidence of acute epiglottitis or a foreign body, the patient’s respiratory status must dictate the extent of further evaluation and treatment. The majority of patients present with a history of mild upper respiratory tract infection and gradual onset of croup. If the Clinical Croup Score21 is less than 4, the child does not appear toxic, there is no respiratory distress and the child does not have stridor at rest, no x-ray or laboratory studies are indicated and the patient may
be discharged home after arrangements are made for mist therapy and the importance of pushing fluids is emphasized. Parents should be encouraged to call or return if there is any question of deterioration, particularly with increasing respiratory distress, cyanosis, drooling, agitation or stridor. Obviously, this approach must be modified if there are communication, compliance, or transportation problems. If the child has stridor at rest, evidence of exhaustion, toxicity, or respiratory distress, admission should be facilitated. The hallmark of management remains mist therapy with close and ongoing observation. Racemic epinephrine (Micronephrine 2%) has been clearly demonstrated to be beneficial.22-2a The solution is mixed so that 0.5 mL is placed in a nebulizer with 2.5 mL of normal saline and administered with or without IPPB over 8 to 15 min. Improvement of symptoms should be rapidly noted with a duration of action of 1 to 2 hours. The treatments may be repeated as needed but are contraindicated in children with cardiac outlet obstructions. Because of the consistent rebound in symptoms, all patients requiring racemic epinephrine should be admitted.23-29 Steroids remain controversial but have been used by many clinicians with impressive success in children with croup symptoms. Dexamethasone 0.30 to 0.50 mg/kg/dose is given parenterally every 6 hours.30~3r~32 It is generally indicated in children requiring racemic epinephrine. Fluid intake should be encouraged.
Table 2. Clinical Croup Score Score Clinical Parameter
0
lnspiratory breath sounds Stridor Cough Retractions and flaring
Normal None None None
Cyanosis
None
Source:
Downes J, Raphaely
R: Pediatric
intensive
1 Harsh with rhonchi lnspiratory Hoarse cry Flaring and supersternal retractions In air care. Anesthesiology
2 Delayed lnspiratory and expiratory Bark As under 1 plus subcostal, intercostal retractions In 40% 0, 1975; 43:242
Jeffrey L. Goldhagen
10
Patients with spasmodic or allergic croup respond dramatically to racemic epinephrine with total resolution of signs and symptoms. However, such patients should be admitted after their initial treatment because of the potential for rebound of symptoms post treatment. If a child with croup presents with a definite history of aspiration of a foreign body, bronchoscopy should be arranged and fluoroscopy performed, assuming that no acute upper airway obstruction exists. If the history is equivocal, fluoroscopy should be initially performed. A positive study will reveal asymmetric movement of the diaphragm on inspiration. Inspiratoryexpiratory PA chest x-ray studies and right and left lateral decubitus chest x-ray studies looking for asymmetric air trapping and shifts of the mediastinum are not usually reliable enough to use as the sole diagnostic tools. Physical examination may reveal wheezing or distinct asymmetry of breath sounds. The history of a prolonged course of croup or the gradual onset of symptoms are both consistent with the diagnosis of foreign body aspiration. If the patient is not responding or has an unusual course, direct laryngoscopy (or bronchoscopy) should be considered to evaluate for bacterial subglottitis (tracheitis), most commonly caused by Staphylococcus aureus. There are no roentgenograph or laboratory investigations that will differentiate bacterial from viral subglottitis. 15If mucosal edema and copious purulent material are noted, the child should be cultured, methicillin (or equivalent) 100
mg/kg/24 h every 4 hours intravenously begun and intubation considered. If improvement of croup symptoms in the child with viral disease is not forthcoming after initiating routine measures, active airway management may be necessary. Only 2-5% of hospitalized children with subglottic obstruction will require airway management, the preferred procedure being nasotracheal intubation. Downes’ score may be used21 to help determine the severity of respiratory distress (Table 2). Oxygen without intubation is rarely indicated since hypoxia serves as one indicator for assessing airway patency and ventilation/perfusion abnormalities limit improvement with oxygen administration. The child should also be evaluated for pulmonary edema and cardiac failure.
Summary
Airway obstruction represents a true medical emergency. The child with croup has some degree of airway obstruction and must be individually and carefully assessed. Special considerations must be given to the infant’s relatively small airway and the generalized nature of the abnormal pathology. Diagnosis, treatment and triage of the patient with subglottic airway obstruction may then be appropriately initiated. Acknowledgement-X-rays
courtesy of Shashikant Sane, MD, Minneapolis Medical Center, and William Cranley, MD, Boston City Hospital.
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5. Loughlin Cl, Taussig L: Pulmonary function in children with a history of laryngotracheobronchitis. J Pediat 1979; 94:365. 6. Taussig L: Clinical and physiologic evidence for the persistence of pulmonary abnormalities after respiratory illnesses in infancy and childhood. Pediatr Res 1977; 11:216. 7. Oswalt C, Gates G, Holstrom F: Pulmonary edema as a complication of acute airway obstruction. JAM4 1977; 238:1833. 8. Travis K, Todres I, Shannon D: Pulmonary ede-
Croup: Pathogenesis
and Management
ma associated with croup and epiglottitis. Pediatrics 1977; 59695. 9. May H, Tittsler R: Laryngotracheitis in chickens. J Amer Vet Med Asso 1925; 67~229. 10. Brighton G: Laryngotracheobronchitis. Ann Otorhinolatyng 1940; 49: 1070. 11. Rabe E: Infectious croup, I, Etiology. Pediatrics 1948; 2:255. 12. Rabe E: Infectious croup, III, Hemophilus influenzae type B croup. Pediatrics 1948; 2:559. 13. Howard J, McCracken G, Luby J: Influenza A2 virus as a cause of croup requiring tracheotomy. J Pediatr 1972; 81:1148. 14. Jones R, Santos J, Overall J: Bacterial tracheitis. JAMA 1979; 242:721. 15. Liston S, Gehrz R, Jarvis C: Bacterial tracheitis. Arch Otolaryng 1981; 107:561. 16. Helfinaer D: Croun vs. enialottitis vs. tracheitis. JAMA-1981; 246:iO87. - 17. Capitanio M, Kirkpatrick J: Obstructions of the upper airway in children as reflected on the chest radiograph. Radiology 1973; 107:159. 18. Mills J, Spackman T, Borns P, Mandell G, Schwartz W: The usefulness of lateral neck roentgenograms in LTB. Amer J Dis Child 1979; 133: 1140. 19. DeLevie M, Nogrady M, Spence L: Acute LTB (croup): Correlation of clinical severity with radiologic and virologic findings. Ann Radiot 1971; 15:193. 20. Newth C, Levison H, Bryan A: The respiratory status of children with crouu. J Pediatr 1972: 82: 1068. 21. Downes J, Raphaely R: Pediatric intensive care. Anesthesiology 1975; 43:242.
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22. Grodin M: Epiglottitis. J Emerg Med 1983; 1: 13. 23. Corkey C, Barker G, Edmonds M, Mok P, Newth C: Radiographic tracheal diameter measurements in acute infectious croup: An objective scoring system. Crit CareMed 1981; 9:587. 24. Lenney W, Mimer A: Treatment of acute viral croup. Arch Dis Child 1978; 53:704. 25. Westley C, Cotton E, Brooks J: Nebulized racemic epinephrine by IPPB for the treatment of croup. Amer JDk Child 1978; 132:484. 26. Singer 0, Wilson W: Laryngotracheobronchitis: Two years’ experience with racemic epinephrine. CanadMAssn J 1976; 115:132. 27. Taussig L, Castro 0, Beaudry P, Fox W, Burean M: Treatment of LTB (croup), use of intermittent positive-pressure breathing and racemic epinephrine. Amer J DtLsChild 1975; 129:79. 28. Gardner G, Powell K, Raden V, Cherry J: The evaluation of racemic epinephrine in the treatment of infectious croup. Pediatrics 1973; 52:52. 29. Adair J, Ring W, Jordan W, Elwyn R: Ten year experience with IPPB in the treatment of acute LTB. Anesth Ann 1971; 50649. 30. Hawkins D: Corticosteroids in the management Otolaryng Head of laryngotracheobronchitis. Neck Surg 1980; 88:207. 31. Tunnessen W, Feinstein A: The steroid-croup controversy: An analytic review of methodologic problems. J Pediafr 1980; 96:751. 32. Leipzig B, Oski F, Cummings C, Stockman J, Swender P: A prospective randomized study to determine the efficacy of steroids in treatment of croup. J Pediatr 1979; 94: 194.