586 SECTION V Pediatric Critical Care Pulmonary lung volumes and pulmonary compliance occurs as the disease progresses, leading to pulmonary fibrosis 1 Expiratory flow rates are usually preserved in p[.]
586 S E C T I O N V Pediatric Critical Care: Pulmonary • BOX 52.1 Etiology of Pediatric Interstitial Lung Disease Infectious • • • • • • • Bacteria Virus Mycoplasma Chlamydia Rickettsia Protozoa Fungus Noninfectious • • • • • • • • • • • • • • • • • • • • • • • • • • • • Acute lung injury Chemical agents Physical agents Radiation Drugs Congenital lymphangiectasia Metabolic disorders Bronchopulmonary dysplasia Hypersensitivity pneumonitis Cardiovascular causes Collagen/vascular disorders Mixed connective tissue disorders Idiopathic pulmonary fibrosis Pulmonary hemorrhage syndromes Pulmonary hemosiderosis Pulmonary venoocclusive disease Desquamative interstitial pneumonia Lymphocytic infiltrative disorders Lymphocytic interstitial pneumonitis Familial erythrophagocytic lymphohistiocytosis Angioimmunoblastic lymphadenopathy Sarcoidosis Inherited diseases Malignancy Leukemia Hodgkin disease Non-Hodgkin lymphoma Histiocytosis X lung volumes and pulmonary compliance occurs as the disease progresses, leading to pulmonary fibrosis.1 Expiratory flow rates are usually preserved in persons with pneumonitis involving the lung parenchyma, and major obstructive defects, although reported, are rare Diffusion capacity, one of the earliest and most sensitive tests of parenchymal inflammation, is diminished in persons with interstitial lung disease (ILD) A reduction in diffusion capacity is not specific and may be found with other parenchymal disorders Early in the course of parenchymal disease, resting arterial oxygen tension may be normal, but there is often mild alveolar hyperventilation with reduction in alveolar carbon dioxide tension and widening of the alveolar-arterial oxygen gradients (Pao2 – Pao2) With exercise, hypoxemia and an increased Pao2 – Pao2 become exaggerated because of ventilation/perfusion (V/Q) imbalance V/Q mismatch is attributed to regional alterations of flow, altered parenchymal compliance, and increased obstruction to pulmonary airflow Progressive alveolitis and subsequent derangement of gas exchange lead to deterioration of ventilatory efficiency and markedly increased work of breathing Adequate oxygenation may become impossible even with the use of high-flow supplemental oxygen Resting hypercapnia, pulmonary hypertension, and eventual right ventricular dysfunction with heart failure are common sequelae.1–4 Diagnosis Diagnosing parenchymal lung disease in the pediatric patient may be quite challenging because of extreme variability in the presentation of disease Clinical evaluation of the child should include a search for symptoms and signs associated with pulmonary disease, such as difficulty with feeding, exercise intolerance, chest pain, cough, tachypnea, dyspnea, cyanosis, orthopnea, clubbing of the nail beds, weight loss, and lethargy In the child with diffuse alveolar disease, auscultative findings may be normal unless significant consolidation or small airway involvement is present Fine crackles that may be heard throughout the chest late in inspiration are a characteristic finding of small airway disease These rales are produced by the opening of occluded small peripheral airways Laboratory Diagnosis The chest radiograph is critical in the diagnosis and management of pulmonary parenchymal disease In children with ILD the classic radiographic features that are present in adults may be absent Computed tomography scanning,5–7 gallium lung scanning, and bronchoalveolar lavage (BAL)8–10 are useful techniques in the diagnosis and management of diseases involving the lung parenchyma Pulmonary function testing is important and usually can be performed reliably in children who are older than years.1,11 Bacterial Pneumonitis Bacterial infections of the lower respiratory tract continue to account for a significant number of hospital admissions The frequency of bacteria as etiologic agents of lower respiratory tract infection varies from 10% to 50% depending on the study population and methods of evaluation used.12,13 In a large study of pediatric patients with lower respiratory tract infections, an etiologic agent was identified in nearly 50% of the patients Bacteria accounted for 10% to 15% of the causative agents identified Factors predisposing to bacterial pneumonia include having numerous siblings, smoke exposure, preterm delivery, living in an urban environment, and poor socioeconomic status Hospitalization also increases the risk of contracting bacterial pneumonia because of the clustering of ill patients in confined areas, administration of immunosuppressive therapy, and various medical and surgical interventions that enhance the opportunity for colonization and infection Additional factors that increase susceptibility to bacterial pneumonia include the presence of an airway foreign body,14 impaired immune response,15–19 congenital and anatomic lung defects, abnormalities of the tracheobronchial tree, cystic fibrosis,20 and congestive heart failure Definition Bacterial pneumonia is an inflammatory process of the lungs that may involve interstitial tissue and pleura in its evolution but always progresses to alveolar consolidation Pathophysiology Pneumonia occurs when pulmonary defense mechanisms are disrupted and bacteria invade the respiratory system by aspiration CHAPTER 52 Pneumonitis and Interstitial Disease or hematogenous spread In most instances pneumonia appears to be a consequence of aspiration of a high inoculum of pathogenic bacteria Viruses are often responsible for enhancing the susceptibility of the respiratory tract to bacterial infection Less frequently, bacterial pneumonia may be the result of defects in host immunity because of young age, underlying immune dysfunction, or immunosuppressive therapy Pneumonia may also occur when host defenses are mechanically disrupted because of tracheostomy or endotracheal intubation The presence of respiratory pathogens in the terminal bronchioles and alveoli induces an outpouring of edema fluid and large numbers of leukocytes into the alveoli.2,21 Macrophages subsequently remove cellular and bacterial debris The infectious process may extend further within the lung segment or disseminate through infected bronchial fluid to other areas of the lung The pulmonary lymphatic system enables bacteria to reach the bloodstream or visceral pleura With the consolidation of lung tissue, VC and lung compliance markedly decrease This leads to intrapulmonary right-to-left shunt and V/Q mismatch, resulting in hypoxia Subsequently, pulmonary hypertension may develop because of significant oxygen desaturation and hypercapnia, often leading to cardiac overload Clinical Features Signs and symptoms of bacterial pneumonia vary with the individual pathogen, age and immunologic condition of the patient, and severity of the illness Clinical manifestations, especially in newborns and infants, may be absent General or nonspecific complaints include fever, chills, headache, irritability, and restlessness Individual patients may have gastrointestinal complaints, including nausea, vomiting, diarrhea, abdominal distention, or pain Specific pulmonary signs include nasal flaring, retractions, tachypnea, dyspnea, and, occasionally, apnea Tachypnea is the most sensitive index of disease severity The sleeping respiratory rate is often a valuable guide to diagnosis On auscultation, diminished breath sounds are frequently noted Fine crackles that may be heard in children and older patients are commonly absent in infants Because of the relatively small size of the child’s thorax and thin chest wall, broad transmission of breath sounds occurs, and the classic findings of consolidation are often obscured Pleural inflammation may be accompanied by chest pain at the site of inflammation This pleuritic pain may cause “splinting,” which restricts chest wall movement during inspiration and reduces lung volume Extrapulmonary infections that may be present in some children include abscesses of the skin or soft tissue (Staphylococcus aureus); conjunctivitis, sinusitis, otitis media, and meningitis (Streptococcus pneumoniae or Haemophilus influenzae); and epiglottitis (H influenzae) Radiographic Features Bacterial pneumonia is typically characterized by defined areas of consolidation with either segmental or lobar involvement Lobar consolidation is the most characteristic, but multilobed disease is not unusual The findings of pleural effusion, pneumatocele, or abscess are also strongly indicative of a bacterial infection Staphylococcal pneumonia is suggested by the rapid clinical and radiographic progression of disease, particularly in a young infant Evidence of an abscess or pneumatocele further suggests a diagnosis of staphylococcal or gram-negative pneumonia, such as Klebsiella Group A streptococcal pneumonia may initially present with a diffuse interstitial 587 pattern before the development of consolidation Except for Pseudomonas, which may have a diffuse nodular appearance in the lower lobes, pneumonias caused by gram-negative organisms have no specific radiographic pattern Anaerobic pulmonary infection is also associated with lung abscesses and air-fluid levels Diagnosis Bacterial pneumonia is suggested by fever, leukocytosis (.15,000 white blood cells), and increased band forms on the peripheral blood smear Examination of the sputum may be helpful in establishing the diagnosis of bacterial pneumonia; however, it is often difficult to obtain a satisfactory sputum sample in pediatric patients unless transtracheal aspiration or bronchoscopy is used Transtracheal aspiration, although useful in adolescents and adults, is associated with significant complications in infants and young children If a sputum sample is obtained (an adequate specimen must have more than 25 polymorphonuclear cells and fewer than 25 epithelial cells per high-power field), the Gram stain should be examined for a predominant bacterial pathogen and cultures should be performed with the appropriate antibiotic susceptibility studies Bacterial pneumonia is accompanied by bacteremia in a significant number of cases; hence, blood cultures should be obtained before initiation of antibiotic therapy Circulating antigens in S pneumoniae and H influenzae may be detected in the blood with counterimmune electrophoresis (CIE),22 polymerase chain reaction (PCR),23–25 or latex agglutination.26,27 If a significant pleural effusion is present, a diagnostic thoracentesis should be performed for the purposes of Gram stain and culture Culturing pleural fluid has a relatively high yield in patients who have not received previous antibiotic therapy If the Gram stain of pleural fluid is negative, CIE or latex agglutination should be performed because bacterial antigen may be detected in the fluid even after the initiation of antibiotics BAL should be considered in the management of a severely ill child in order to make a prompt diagnosis.9,10 Making a prompt diagnosis is essential for the patient with progressive disease who has responded poorly to initial therapy or for the child with underlying immunodeficiency for whom empiric antibiotic treatment may be hazardous In such instances, if the BAL is nondiagnostic, then lung aspiration or biopsy should be considered.28 Material may be obtained through closed-needle biopsy, percutaneous needle aspiration, or an open-lung biopsy Positive results for such procedures in carefully selected cases identify an etiologic agent in 30% to 75% of cases, with open-lung biopsy having the highest yield.18,29 Specific Pathogens Group B Streptococci Group B streptococci can cause infection in people of any age; however, these organisms are common pathogens in infants younger than months.30 Early-onset illness is often associated with maternal fever at the time of delivery, prolonged rupture of membranes, amnionitis, prematurity, and low birth weight Infected neonates usually manifest clinical symptoms within the first to 12 hours of life Symptoms include fever, respiratory distress, apnea, tachypnea, and hypoxemia By 12 to 24 hours of age, signs of cardiovascular collapse are often apparent Frequently, the syndrome of pulmonary hypertension of the newborn is present, and pulmonary or intracranial hemorrhage may become the terminal event 588 S E C T I O N V Pediatric Critical Care: Pulmonary Isolation of the organism establishes the diagnosis Cultures from blood and cerebrospinal fluids must be obtained in all instances of suspected group B streptococcal pneumonia Rapid diagnostic techniques have been helpful in providing early diagnoses The radiographic findings in neonates with group B streptococcal pneumonia can be either a lobar (40%) or a diffuse reticulonodular pattern with bronchograms similar to findings of respiratory distress syndrome Aggressive cardiovascular and ventilatory support is usually required, particularly in the early stages of the disease Antibiotic therapy should include a combination of ampicillin or penicillin and an aminoglycoside agent Although in the past the mortality rate of patients with group B streptococcal pneumonia could be as high as 50% to 60%, recent studies suggest improvement with prompt initiation of therapy and even better outcomes with maternal prophylaxis.31 Some infants experience a second episode of infection to weeks after discontinuation of antibiotic therapy Infants with group B streptococcal pneumonia and meningeal involvement (30%) may demonstrate significant neurologic deficits (20%–50%) Streptococcus Pneumoniae S pneumoniae is a gram-positive diplococcus with at least 84 sera types; however, 80% of the serious infections are caused by only 12 sera types Streptococci are a major cause of pneumonia in the United States, usually affecting infants younger than years, with a peak age between and months Patients with asplenia, functional hyposplenia, or malignancy or those receiving immunosuppressive drugs are at special risk of the development of invasive disease.32 The radiographic finding in infants is often a patchy bronchopneumonia Lobar consolidation is not uncommon Penicillin is the drug of choice in the treatment of persons with streptococcal pneumonia However, organisms relatively resistant to penicillin occur in 3% to 40% of culture-positive patients recorded in studies from different parts of the United States.33 In such instances pneumonias have been effectively treated with vancomycin or high-dose b-lactam cephalosporin agents, such as cefuroxime, ceftriaxone, or cefotaxime Disease resulting from penicillin-resistant pneumococci should be considered in patients who received therapy with b-lactam antibiotics.33–35 The pneumococcal 13-valent conjugate vaccine is recommended for all children aged years and younger It is also recommended for certain children aged 60 to 71 months with chronic medical conditions, immunosuppressive conditions, functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants The pneumococcal polysaccharide vaccine, a 23-valent formulation, is recommended in children years and older with an increased risk of invasive pneumococcal disease.36 Haemophilus Influenzae Haemophilus organisms are small, nonmotile, gram-negative rods that occur in both encapsulated and nonencapsulated forms Approximately 90% to 95% of invasive disease is caused by the encapsulated sera type B A pleural effusion or empyema is detected in nearly 40% of patients with H influenzae pneumonia There is an extremely high incidence of bacteremia in this disease Serious complications—such as epiglottitis, meningitis, and pericarditis— can be diagnosed in 15% to 20% of patients Cellulitis, anemia, and septic arthritis occur infrequently In a hospitalized patient, administration of b-lactam agents or a second- or third-generation cephalosporin is generally an effective therapy.33,37 The mortality rate in appropriately treated patients is generally considered to be less than 5% and often is related to associated meningitis, epiglottitis, or pericarditis rather than the pneumonic process itself Hib conjugate vaccine is an important measure in reducing the incidence of Haemophilusrelated disease and should be administered to all children.33,38,39 Staphylococcal Pneumonia Primary S aureus pneumonia has decreased in frequency in recent years but still accounts for approximately 25% of cases in young infants The incidence of secondary or metastatic dissemination has increased since 1972 Patients with primary pneumonia present with fever and respiratory symptoms, whereas those with metastatic disease often present with fever, generalized toxicity, and musculoskeletal symptoms In patients presenting with primary staphylococcal pneumonia, the disease is often preceded by an upper respiratory tract infection.40 Pleural effusion or empyema develops in nearly 80% of the patients with primary staphylococcal pneumonia and is extremely common in patients with metastatic disease It is not unusual for patients with staphylococcal pneumonia to remain bacteremic long after the initiation of appropriate antibiotic therapy Radiographic findings of S aureus pneumonia differ according to the stage of the disease They vary from minimal changes to consolidation (most common) and are associated with pleural effusion (50%–60%) or pneumothorax (21%) Pneumatoceles usually appear during the convalescent stage and may persist for prolonged periods in asymptomatic patients Antibiotic therapy should be administered intravenously and include a drug that is resistant to inactivation Strong consideration should be given to providing antibiotic coverage for methicillin-resistant S aureus, which can account for 1% to 30% of isolates depending on the prevalence in the area.40 The duration of therapy is usually lengthier in patients with staphylococcal disease than for patients with other bacterial pneumonias and consists of 21 days or more of treatment The mortality rate of staphylococcal pneumonia varies from 23% to 33% Increased mortality is usually associated with younger age, inappropriate initial antimicrobial therapy, or failure to drain an empyema appropriately Mycoplasma Pneumonia Mycoplasma organisms are the smallest free-living microorganisms They lack a cell wall and are pleomorphic Mycoplasma is an uncommon cause of pneumonia in children younger than years but is the leading cause of pneumonia in school-aged children and young adults Illness can range from a mild upper respiratory tract infection to tracheobronchitis to pneumonia Symptoms include malaise, low-grade fevers, and headache In 10% of children a rash develops that usually is maculopapular Cough, if it develops, usually occurs within a few days and may continue for to weeks Initially the cough is nonproductive but then may become productive and is usually associated with widespread rales on physical examination Radiographic abnormalities vary but are usually bilateral and diffuse.41 Isolation of Mycoplasma by culture is complicated by the requirement for special enriched broth or agar media, which are not widely available It is successful in only 40% to 90% of cases and requires to 21 days A fourfold increase in antibody titer between acute and convalescent sera is diagnostic, but the time involved is lengthy, providing only a retrospective diagnosis Complement fixation and immunofluorescent and several enzyme immunoassay antibody tests have been developed but are CHAPTER 52 Pneumonitis and Interstitial Disease of limited diagnostic value.33 Serum cold agglutinins with titers of 1 : 32 or greater are present in more than 50% of patients with pneumonia by the beginning of the second week of illness The PCR test has become an important means of diagnosing M pneumoniae infections in clinical practice, allowing for initiation of therapy directed at the causative pathogen.41 Treatment of upper respiratory tract infections or acute bronchitis is rarely indicated, but treatment with erythromycin or another macrolide, such as azithromycin, is indicated for persons with pneumonia or otitis media Gram-Negative Bacteria Pneumonia caused by gram-negative enteric bacteria, especially Pseudomonas, is almost always found in patients with underlying pulmonary disease, compromised immune status, or those receiving prolonged respiratory therapy.42,43 Gram-negative enteric bacteria are a frequent cause of nosocomial infection in critical care units These organisms can produce a severe necrotizing pneumonia that is associated with an increase in morbidity.44 Legionella Pneumophila Pneumonia caused by Legionella pneumophila has been reported infrequently in the pediatric age group.45–48 The onset of this disease is characterized by high, unremitting fever; chills; and a nonproductive cough.46 Extrapulmonary manifestations include gastrointestinal symptoms such as diarrhea, liver involvement, and confusion Chest radiographs typically consist of peripheral nodular infiltrates and pleural effusions Cavitation occurs only in immunosuppressed individuals Death in the normal host is unusual if prompt therapy with azithromycin or erythromycin is initiated Anaerobic Bacteria Pneumonia resulting from anaerobic upper respiratory flora is uncommon in healthy children When it does occur, it is frequently associated with risk factors such as underlying pulmonary disease, a central nervous system (CNS) disorder (including seizures), a postanesthetic state, and aspiration of a foreign body Lung abscess and empyema are frequent complications in persons with anaerobic bacterial pneumonias Complications The mortality rate in persons with uncomplicated bacterial pneumonia is less than 1% Death is more common in children with a complicated disease or an underlying disorder The most frequent complications of bacterial pneumonia are pleural effusion and empyema (Table 52.1) Thoracentesis should be performed if fluid is present to facilitate an etiologic diagnosis and establish the character of the fluid Tube thoracostomy is indicated if a large amount of fluid is present and causes respiratory compromise or if purulent fluid is obtained by thoracentesis Empyema may extend locally to involve the pericardium, mediastinum, or chest wall Evidence of empyema extension should be considered in the child who is unresponsive to antibiotic therapy.28 When tube thoracostomy/surgical drainage is required, it should be discontinued as soon as drainage has substantially decreased For patients with staphylococcal empyema, streptococcal pneumonia, or H influenzae empyema, to days of drainage is usually sufficient Patients with empyema require prolonged antimicrobial therapy and careful follow-up 589 TABLE Major Sequelae/Life-Threatening Complications 52.1 Associated With Bacterial Infections Complication/Sequelae Organism Necrotizing pneumonia Anaerobic, GNB Respiratory failure GBS Shock GBS, SP, H influenzae, GNB Apnea GBS Pneumothorax H influenzae Pneumatoceles H influenzae, anaerobic, staph, SP, GAS Abscess (lung) Staph, SP, anaerobic Pleural effusion H influenzae, GAS, SP, staph Empyema H influenzae, staph, SP Epiglottitis H influenzae, GAS Meningitis H influenzae, GBS, SP Encephalopathy Legionella Pericarditis H influenzae Bone/joint H influenzae, staph Kidneys Staph GAS, Group A streptococcus; GBS, group B streptococcus; GNB, gram-negative bacteria; SP, Streptococcus pneumoniae; staph, Staphylococcus aureus Pneumothorax and pneumatoceles can be seen with almost any bacterial pneumonia but are especially common with staphylococcal disease.49 Such pneumatoceles require no special therapy and usually resolve Lung abscess is an infrequent complication of H influenzae and pneumococcal pneumonia and is most often encountered with staphylococcal disease or anaerobic bacteria Prognosis is usually excellent, even in persons with severe bacterial pneumonia complicated by empyema Long-term follow-up of children with empyema has demonstrated remarkably few if any residual pulmonary function abnormalities and remarkable clearing of chest radiographs In contrast to adults with empyema, children seldom require surgical procedures such as decortication However, follow-up chest radiographs should be obtained on all patients with bacterial pneumonia to document complete resolution Such radiographic follow-up studies are probably not indicated until at least to weeks following the initiation of antibiotic therapy Therapy Therapy for persons with bacterial pneumonia should include appropriate IV antibiotic treatment directed toward the specific pathogen if it is known (Table 52.2) Localized or compartmental complications—such as empyema, lung abscess, pericarditis, or septic joints—require appropriate surgical drainage and antibiotic therapy Prevention via immunization or chemoprophylaxis has changed the incidence and epidemiology of pneumonitides significantly Options for immunization, active or passive, and chemoprophylaxis for various etiologic agents are listed in Table 52.3 590 S E C T I O N V Pediatric Critical Care: Pulmonary TABLE Bacterial Pneumonia Therapy 52.2 Disease/Organism Therapy Undetermined Organisms Serious, life-threatening pneumonia, nonsuppressed host Cefotaxime or ceftriaxone azithromycin vancomycin Bronchial lavage or needle aspiration of lung may be necessary to establish diagnosis Suppressed neutropenic host Imipenem/meropenem or piperacillin or ceftazidime aminoglycoside clindamycin Vancomycin not included in initial therapy unless high suspicion or if patient has indwelling line Amphotericin not used unless still febrile after days/high suspicion Bronchial lavage, needle/open biopsy may be necessary to establish diagnosis Lung abscess Clindamycin or ticarcillin/clavulanate or piperacillin/tazobactam Specific Organisms Pneumonia With Empyema Streptococcus pneumoniae, group A strep Penicillin susceptible Preferred: ampicillin or penicillin chest tube drainage Alternative: ceftriaxone or cefotaxime chest tube drainage Penicillin resistant Preferred: ceftriaxone chest tube drainage Alternative: ampicillin (increased dosing), levofloxacin or linezolid chest tube drainage Staphylococcus Methicillin sensitive Preferred: cefazolin, nafcillin or oxacillin chest tube drainage Alternative: clindamycin or vancomycin chest tube drainage Methicillin resistant Preferred: vancomycin chest tube drainage Alternative: linezolid chest tube drainage Pneumonia Without Empyema Haemophilus influenzae Preferred: ampicillin or cefotaxime or ceftriaxone Alternative: ciprofloxacin or levofloxacin Klebsiella pneumoniae Meropenem until susceptibilities are available Escherichia coli, Enterobacter Aminoglycoside or cephalosporin Legionella Preferred: azithromycin or erythromycin Alternative: ciprofloxacin or levofloxacin Pseudomonas Aminoglycoside anti-Pseudomonas penicillin or aminoglycoside ceftazidime Mycoplasma pneumoniae Preferred: azithromycin Alternative: erythromycin or levofloxacin TABLE Preventive Measures 52.3 Organism Immunization Chemoprophylaxis Cytomegalovirus IVIG: prophylaxis in seronegative transplant recipients Ganciclovir or valganciclovir Haemophilus influenzae type B Capsular polysaccharide vaccine or conjugate vaccine Cefotaxime or ceftriaxone Influenza Inactivated virus produced in chicken embryos Oseltamivir (A or B) or zanamivir (A or B) Measles Live virus vaccine or IVIG for immunocompromised patients None Streptococcus pneumoniae Capsular polysaccharide antigens of 13 or 23 pneumococcal serotypes vaccine or pneumococcal conjugate vaccine Penicillin VK for functional or anatomic asplenia until age y Pneumocystis carinii None Trimethoprim-sulfamethoxazole or pentamidine or dapsone or atovaquone RSV Palivizumab (monoclonal antibody) None Group B strep None Intrapartum antibiotics IVIG, Intravenous immunoglobulin; RSV, respiratory syncytial virus; strep, Streptococcus spp ... antibiotic coverage for methicillin-resistant S aureus, which can account for 1% to 30% of isolates depending on the prevalence in the area.40 The duration of therapy is usually lengthier in patients... drainage Staphylococcus Methicillin sensitive Preferred: cefazolin, nafcillin or oxacillin chest tube drainage Alternative: clindamycin or vancomycin chest tube drainage Methicillin resistant Preferred:... patients are commonly absent in infants Because of the relatively small size of the child’s thorax and thin chest wall, broad transmission of breath sounds occurs, and the classic findings of consolidation