chronic lung Disease of the newborn
cHaPTer ouTline
INTRODUCTION
You have now acquired 2 years of experience as a respiratory therapist, and during this time, you have spent much of it with adult patients who have probably been diagnosed with chronic obstructive pulmonary dis- ease (COPD). In the time that you will spend understanding neonatal/
pediatric respiratory care, you will encounter a little patient that reminds you of a COPD patient.
DEFINE
Chronic lung disease of the newborn (CLD), also historically known as bronchopulmonary dysplasia (BPD), was first described by Northway et al. in 1967 as “a chronic respiratory disease that developed in premature infants exposed to mechanical ventilation and oxygen supplementa- tion.”1 In 2001, a workshop conducted by the National, Heart, Lung, and Blood Institute (NHLBI) proposed a severity-based definition for infants younger than 32 weeks.2 This definition more accurately defined CLD:4
Mild BPD was defined as a need for supplemental oxygen for greater than or equal to 28 days but not at 36 weeks postmen- strual age or discharge; moderate BPD was defined as oxygen for greater than or equal to 28 days plus treatment with less than 30% oxygen at 36 weeks postmenstrual, and severe BPD was defined as oxygen for greater than or equal to 28 days plus greater than or equal 30% oxygen and/or positive pressure at 36 weeks postmenstrual.
Who is affected by clD?
NHLBI reports that between 5,000 to 10,000 babies born each year will develop, CLD.3 Additionally, Eugenio Baraldi and Marco Filippone sug- gest that there are nearly 60,000 infants born each year in the United States under 1500 grams (about 3.5 pounds), and about 20% of them will develop CLD.1
DESCRIBE
Chronic lung disease of the newborn can be described as a significant lung change in a premature infant who is diagnosed with respiratory
distress syndrome (RDS), requiring mechanical ventilation and/or high concentrations of inspired oxygen. This change results in the potential for impaired gas exchange, lung collapse, inflammation to the lung tis- sue, and overall pulmonary dysfunction.
The following are classic signs of CLD:5
History of prematurity that required the use of mechanical ventila-
• tion or the inability to wean from the ventilator Oxygen dependency
• Tachypnea, retractions, nasal flaring
• Feeding intolerance
• Poor tolerance to being touched
•
Breath sounds that indicate crackles and diminished air entry
• More susceptible to lung infections, especially respiratory syncytial
• virus (RSV)
Respiratory syncytial virus itself is a medium-sized RNA virus and is
•
classified as a paramyxovirus.5,6 RSV begins in the nasal epithelial cells and then replicates itself in the host cell, ultimately destroy- ing the host cell, giving it the ability to reproduce in uninfected cells.
Frequent visits to the hospital before the age of 2 years
•
CLD, as described by Kacmarek et al. (2005), can be categorized in stages based on the infant’s age and the severity of the condition:5
Stage 1
•
Occurs during the first 3 days of life
• Chest x-ray shows a ground-glass appearance and air broncho-
• grams Stage 2
•
Occurs at about 4 days up to 10 days of life
• Formation of hyaline membrane
• Granular opacification of the lungs, which makes it difficult to
• distinguish the heart borders Stage 3
• • Occurs at 10 to 20 days of life
Transition from acute to the chronic phase of CLD
•
Lung “whiteout” with multiple small cysts on chest x-ray
•
Alveolar emphysema and interstitial fibrosis
• Evidence of congestive heart failure
• Stage 4
• • Occurs after 28 days of life Large, irregular cysts on chest x-ray
• Hyperinflation, flattened diaphragm, and evidence of atelectasis
• Thickened alveolar walls and increased diffusion gradient
• Prominent ventilation and perfusion mismatching
•
Slow wean from mechanical ventilation
•
DISTINGUISH
Care must be made to distinguish CLD from other chronic respiratory ill- nesses. Asthma and bronchiolitis can present with similar clinical symp- toms in children under 2 years. In children over two years, gastric esoph- ageal reflux is another condition that mimics asthma. A careful medical history with concurrent physical examination and required laboratory testing will help to determine the appropriate diagnosis. CLD must be distinguished from the following:
Asthma—a chronic inflammation of the airways with reversible epi-
• sodes of obstruction caused by an increased reaction of the airways to various stimuli.7
Bronchiolitis—an acute, highly infectious lower respiratory tract
•
infection caused mainly by the respiratory syncytial virus (RSV).5 Gastric esophageal reflux disease (GERD)—the regurgitation of stom-
• ach contents into the esophagus. This condition is more prevalent in children with a diagnosis of asthma. This condition worsens asthma symptoms. Children with CLD have difficulty with eating and are often placed on GERD precautions to monitor the potential for aspi- ration pneumonia.
RESEARCH
Since Norway and his colleagues described CLD in 1967, there has been a plethora of research on CLD. Although Norway and his research team
proposed that CLD was caused by the initiation of mechanical ventila- tion and the use of oxygen therapy in the preterm infant, this devel- opment occurred prior to the development and implementation of sur- factant in the clinical setting. Current research suggests that there is a distinction between “new CLD” and “old CLD.”1,3 The pathophysiology of old CLD demonstrates significant airway injury, inflammation, and lung tissue fibrosis compared to the new CLD, in which there is less lung tissue fibrosis, less airway injury, less inflammation, and more uniform inflation.1,3
CLD is not as common as it once was, due in part to the use of bet- ter ventilator techniques, the use of steroids before birth, and the use of surfactant therapy.3 Infants who develop CLD tend to be premature, lack surfactant, have very low birth weight, and exhibit little to no lung injury at birth; however, they subsequently develop oxygen dependency over the course of their stay in the nursery.
The goals of the workshop sponsored by NHLBI were to develop an accurate definition of CLD, review the literature, and make recommenda- tions for future research. With respect to future research, the members of the NHLBI workshop suggest the following research priorities:3,6
Understand the development biology of the lung structure
• Understand how inflammation and injury are expressed by the devel-
• oping lung
Establish a resource tissue bank
•
Develop new clinical tests for lung function in infants and children
• Study genetic contribution to the development of CLD
• Develop standards of care as a basis of clinical trials
• Evaluate delivery room procedures and ventilation techniques
•
Evaluate nutrition, antioxidant, and anti-inflammatory interventions
• Train physicians and physiologists with expertise in evaluating lung
• function in infants and children
Although CLD is occurring less frequently, it continues to develop in 20% of low birth weight infants born in the United States. Infants with CLD utilize a considerable amount of healthcare services, making CLD one of the most chronic respiratory illnesses in children younger than 2 years old.3 Research suggests that the best method of treating children
with CLD is to prevent it from occurring; however, if prevention fails, supportive therapy can help to diminish lung damage and improve over- all pulmonary health in children with CLD.
TREATMENT
Supportive therapy has been shown to be an effective means of treat- ing patients with CLD. Therapeutics used to treat CLD includes oxygen therapy, nutritional support, pharmacology therapy, bronchopulmonary hygiene, and positive pressure ventilation. CLD is such a complex con- dition that it requires multiple treatment regimens in order to manage the chronic respiratory symptoms. The research states that treating CLD should be multifocused.8 Table 4-1 illustrates the various CLD treatment options that are available. One or more therapeutics may be used in the treatment of children with CLD. Proposed strategies for managing chil- dren with CLD will fall into the following categories:
I. Prevention
A. High risk birth—Research indicates that prevention of CLD is the ultimate goal; Walsh et al. conclude that there is a clear evidence that the use of betamethasone in high-risk mothers has been beneficial in the survival of very low birth weight infants.9 B. Antenatal steroids—Early administration of surfactant and gentle
modes of mechanical ventilation have been shown to minimize lung injury.8
II. Ventilator and Oxygen Strategy
A. Oxygen therapy—For severe CLD patients who remain on supple- mental oxygen for more than 30 days.
Keep oxygen saturation in the range of 88% to 92% and a
• partial pressure of oxygen (PaO2) of 50–70 mm Hg. This is considered a conservative use of oxygen in which you strike a delicate balance between promoting adequate oxygenation and decreasing the potential for retinopathy of prematurity.8 Nasal cannula at flows of ẳ liter per minute up to 2 liters per
• minute on a blender, keeping FiO2 between 22% and 40% to keep SpO2 between 88% and 92%.
Table 4-1 CLD Treatment Options Type of Therapy application Oxygen therapy
Nasal cannula Low flow nasal cannula
Goal is to maintain oxygen as low as possible. Keep SpO2 greater than 92%.
Given with a blender to control precise FiO2
Given with a low flow flowmeter if a blender is not available
Regular neonatal and pediatric nasal cannulas are available in varying sizes.
figure 4-1 illustrates a small neonatal nasal cannula. figure 4-2 illustrates a pediatric nasal cannula.
Heated, humidified high flow nasal cannula10,11,12
Used to avoid mechanical ventilation Used to wean patients from mechanical ventilation
High flow nasal cannula has been compared to the use of nasal CPAP; although the mechanics of delivery is known, the actual amount of pressure to the airway is not fully understood10, 11, 12, 13
figure 4-3 is an illustration of a high flow nasal cannula.
High flow oxygen and aerosol therapy
Tracheostomy collar
Goal is to provide oxygen and humidity to the airway. Keep FiO2 as low as possible.
Given with a blender in most nurseries.
Close attention must be paid to CLD patients with tracheostomy tubes.
Potential for respiratory infection Potential for mucus plugging Need for frequent suctioning
figure 4-4 is an illustration of a tracheostomy collar on an infant Mechanical ventilation7
Ventilator strategy includes settings that would maintain adequate PaCO2 and PaO2.
Keep PaCO2 between 40 to 50 mm Hg; may be higher for CLD.
Keep PaO2 between 60 to 80 mm Hg.
Keep SpO2 between 90% to 95% with low oxygen requirements.
Weaning from mechanical ventilation13
The use of nasal CPAP The use of high flow nasal cannula
Nutritional support Adequate nutrition aids in the healing of damaged lung tissue.
Pharmacology therapy Bronchodilator therapy with beta agonist has been shown to help in managing bronchoconstriction.
Inhaled steroids help manage airway inflammation.
Cromolyn sodium is used to prevent mast cell rupture.
Antibiotics for respiratory infections Diuretics for fluid management
fiGure 4-1 Neonatal nasal cannula
fiGure 4-2 Pediatric nasal cannula
fiGure 4-3 High humidity nasal cannula
fiGure 4-4 Tracheostomy collar
High flow nasal cannula at flows of greater than 2 liters per
•
minute, up to 6 liters per minute on a blender, keeping FiO2
between 22% to 40% to keep PaO2 of 50–70 mm Hg and SpO2
88% to 92%.
Although high flow nasal cannulas have become routine
•
therapy in many neonatal and pediatric units, it is neces- sary to describe how the high flow nasal cannula gained its usefulness. By definition, high flow therapy is the deliv- ery of high inspired gas flow that generally exceeds peak inspiratory demand. It is accomplished by warming and humidifying the dry gas at body temperature. Although this concept is not new, the use of high flows with a nasal can- nula is new.14 Waugh et al. evaluated two devices for use in providing high flow therapy through a nasal cannula. Both the Salter lab device and the Vapotherm device met the minimum standards for humidification at the high flows.
The goal of using high flow nasal cannula is to provide oxy- gen liter flows greater the conventional 6 liters per minute.
In the clinical setting, we conveniently compare high flow nasal cannula to the use of nasal CPAP; however, a word of caution: the research has not yet established conclusive evi- dence of measured flow rates in relation to actual pressures to the airway. Additional research is necessary to demon- strate adequate comparison of the high flow nasal cannula to nasal CPAP units.
B. Ventilator management—for severe CLD patients who require ventilatory support post extubation.
Nasal CPAP settings—initial settings 4 to 5 cm H
• 2O. Adjust
pressures in increments of 1 to 2 cm H2O to keep PaCO2 less than 50 mm Hg. FiO2 to keep saturations between 88%
and 92%. There may be instances in which the PaCO2 will be allowed to be higher than 50 mm Hg (called permissive hypercapnia).
Mechanical ventilation—initial settings
•
Common modes available on new generation ventilators
•
include SIMV, assist/control, pressure support ventilation (PSV), and volume guarantee (VG). The choice of mode will depend on the clinician’s experience and clinical judgment.
Ventilator frequency—adjusted to keep PaCO
• 2 40 to 50 mm
Hg; in CLD, PaCO2 may be higher than 50 mm Hg in an ef- fort to protect the lungs from ventilator-associated injury.
Frequency of 40 to 50 breaths/min for infants
• Frequency of 12 to 20 breaths/min for pediatric
•
Ventilator tidal volume—6 to 8 mL/kg for pediatric
• Ventilator tidal volume—4 to 6 mL/kg for infants
• Ventilator PEEP—5 to 8 cm H
• 2O
Ventilator FiO
• 2—to keep saturation greater than 92%; PaO2 between 50 and 70 mm Hg
Keep peak airway pressure (PAP) less than 25 cm H
• 2O if able
to maintain PaCO2 between 40 and 50 mm Hg Goal is adequate chest rise.
•
Avoid overdistention of the lungs.
•
Ventilator inspiratory time—ranges from 0.3 sec to 1 sec
• depending on the size of the child and the results of the arterial blood gas.
III. Pharmacology Strategy
A. Short-acting bronchodilator—has been shown to help manage bronchospasms. Albuterol and levalbuterol (Xopenex) are the two most common short-acting bronchodilators. Both have been shown to be safe when used in both infants and children.
These medications are available in a nebulizer or a metered dose inhaler. Metered dose inhalers are used most often in the treatment of CLD when patients are discharged from either the NICU or PICU. This is of particular importance because medica- tions like fluticasone (Flovent) are often prescribed for ongoing use. Currently, budesonide (Pulmicort) has been prescribed more often for children with CLD, which can be given as a nebulized treatment or metered dose inhaled treatment. Treatment given
as a metered dose inhaler should be given with a holding cham- ber for better deposition.
B. Corticosteroids—Research indicates that steroids have demonstrat- ed a decrease in the incidence of CLD; however, the American Academy of Pediatrics (AAP) has issued a recommendation that corticosteroids should not be used in preterm infants.15 Despite this warning, clinicians continue to use steroids in patients with severe lung injury and those considered ventilator dependent.16 Early research shows that dexamethasone8,9,17 has been used in the treatment of CLD despite the warning by the AAP.
C. Nonsteroidal anti-inflammatory medications—Drugs such as cro- molyn sodium and nedocromil sodium have demonstrated some benefits in preventing mast cell rupture; however, these medica- tions are associated more often with children who have chronic asthma.
D. Diuretics—Lasix has been well documented in the management of fluid-overload.8 In the long-term treatment of children with CLD, thiazide diuretics such as Aldactone have been shown to increase urine output and improve pulmonary functions.8 E. Antibiotics—It has been documented that during the first few
years of life, CLD infants tend to have an increased number of respiratory infections, resulting in the need for good pulmonary toiletry and good hydration. Studies show that Ureaplasma urealyticum has been an indicator of CLD and promotes tissue inflammation and early stages of pulmonary fibrosis.8
F. Table 4-2 illustrates the more common medications used in the treatment of CLD.
IV. Nutrition Strategy
A. Nutritional support—The literature states that nutritional support improves CLD outcomes by reducing the need for supplemen- tal oxygen and the ability to wean quickly from the ventilator.
Children with CLD require an increase in caloric intake. A diet with adequate proteins, fats, carbohydrates, vitamins, and trace minerals helps prevent continued lung injury.8 According to William Driscoll and colleagues, several studies have shown that
Table 4-2 Typical Dosages for Drugs Commonly Used in the Treatment of CLD short-acting bronchodilators
albuterol MDi albuterol Xopenex
Under 5 kg 1.25 mg 1–2 puffs .31 mg
Over 5 kg 2.5 mg 1–2 puffs .63 mg or 1.25 mg (weight
dependent) anticholinergic
Atrovent (ipratropium bromide) can be given as either nebulizer or MDI
nebulizer MDi 18 mcg/puff
Under 5 kg 0.25 mg 2 puffs
Over 5 kg 0.50 mg 2 puffs
Diuretics—prescribed based on weight
Lasix (furosemide) 0.5–2 mg/kg/dose PO or IV BID or QOD (QD in infants less than 31 weeks postconceptual age) Aldactone (Your unit most likely has established guidelines on the dose of this medication.)
antibiotics
Tobramycin—it is recommended to be given after the short-acting bronchodilator to prevent bronchospasms.
Under 5 kg 1 mL or 40 mg with nebulizer
Over 5 kg 2 mL or 80 mg with nebulizer
inhaled steroids
Decadron (dexamethasone) 0.15–0.25 mg/kg/dose by mouth or IV divided BID; wean over 5–7 days.17 Pulmicort (budesonide)—given in a nebulizer—this medication should not be mixed with other medications in the nebulizer.
Under 5 kg 0.25 mg ampule
Over 5 kg 0.50 mg ampule
nonsteroidal anti-inflammatory Intal (cromolyn sodium)
Under 5 kg 1 mL or 10 mg with nebulizer
Over 5 kg 2 mL or 20 mg with nebulizer
Note: This is not an all-inclusive list of the medications that are used for children with CLD. This list represents typical drugs that have been documented as having some benefits in treating the respiratory symptoms in CLD. It is recommended that you refer to a pharmacology book that describes pediatric and infant medications for an in-depth discussion of the various types of medications.
a vitamin A supplement may speed up lung repair mechanism and thereby decrease the incidence of CLD.10
SUMMARy
To summarize, this chapter covered the following facts about chronic lung disease of the newborn:
It is a chronic respiratory disease that affects premature infants
✔
✔
exposed to mechanical ventilation and oxygen therapy.
It affects mainly premature infants who lack surfactant and/or who
✔
✔
have very low birth weight.
It results in impaired gas exchange, lung collapse, and inflamma-
✔
✔ tion.
It is categorized in four stages based on infant’s age and severity.
✔
✔
It requires a multidisciplinary team approach to manage this
✔
✔
chronic condition.
Although CLD is a very complex condition, a child with CLD can be managed well with the right type of therapy. Our expertise as respiratory therapists in the NICU and PICU can make a big difference in helping shape the long-term care plan of these children. Given that we inter- act with these patients from the delivery room to discharge, our role as experts in ventilator management and oxygen therapy can and should make a difference in the lives of children with CLD and their families.
REFERENCES
1. Baraldi, E., & Filippone, M. (2007). Chronic lung disease after premature birth. New England Journal of Medicine, 357 (19), 1946–1955.
2. National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute/Office of Rare Diseases. (2000, June 1–2). Workshop on bronchopulmonary dysplasia, Bethesda, MD.
3. Jobe, A., & Bancalari, E. (2001). Chronic lung disease of the newborn. American Journal of Respiratory and Critical Care Medicine, 163 (7), 1723–1729.
4. Ehrenkranz, R., Walsh, M., Vohr, B., Jobe, A., Wright, L., Fanaroff, A., et al. (2005, December). Validation of the National Institutes of Health consensus definition of chronic lung disease of the newborn. Pediatrics, 116 (6), 1353–1360.
5. Kacmarek, R., Dimas, S., Mack, C. (2005). The essentials of respiratory care (4th ed.). St. Louis, MO: Mosby Elsevier.
6. Walsh, M., Szefler, S., Davis, J., Allen, M., Van Marter, L., Abman, S., et al. (2006). Summary proceedings from the Bronchopulmonary Dysplasia Group. Pediatrics, 117, S52–S56. Retrieved February 22, 2008, from http://www.pediatrics.
org/cgi/content/full/117/3/S1/S52