Pediatric Respiratory Failure 

Updated: Sep 30, 2016
Author: Shelley C Springer, JD, MD, MSc, MBA, FAAP; Chief Editor: Timothy E Corden, MD 

Overview

Practice Essentials

Pediatric respiratory failure develops when the rate of gas exchange between the atmosphere and the blood is unable to match the body's metabolic demands. Acute respiratory failure remains an important cause of morbidity and mortality in children. Cardiac arrests in children frequently result from respiratory failure. See the image below.

Bilateral airspace infiltrates on chest radiograph Bilateral airspace infiltrates on chest radiograph film secondary to acute respiratory distress syndrome that resulted in respiratory failure.

Signs and symptoms

Patients may be lethargic, irritable, anxious, or unable to concentrate. Children with respiratory distress commonly sit up and lean forward to improve leverage for the accessory muscles and to allow for easy diaphragmatic movement. Children with epiglottitis sit upright with their neck extended and head forward while drooling and breathing through their mouth.

The respiratory rate and quality can provide diagnostic information, as exemplified by the following:

  • Bradypnea: Most often observed in central control abnormalities

  • Tachypnea: Fast and shallow breathing is most efficient in intrathoracic airway obstruction; it decreases dynamic compliance of the lung

The patient should also be evaluated for the following:

  • Stridor (an inspiratory sound)

  • Wheezing (an expiratory sound)

  • Crackles

  • Decreased breath sounds (eg, alveolar consolidation, pleural effusion)

  • Paradoxical movement of the chest wall

  • Accessory muscle use and nasal flaring

Cardiovascular signs in patients with respiratory failure can include the following:

  • Tachycardia and hypertension: May occur secondary to increased circulatory catecholamine levels

  • Gallop: Suggestive of myocardial dysfunction leading to respiratory failure

  • Bradycardia: Age-specific bradycardia associated with decreased or shallow breathing and desaturations indicates the need for emergent positive-pressure ventilation

See Clinical Presentation for more detail.

Diagnosis

Blood and pulmonary studies

  • Arterial blood gas (ABG) measurement: Can be used to define acute respiratory failure

  • Complete blood count (CBC): Polycythemia suggests chronic hypoxemia

  • Electrolyte abnormalities: Hypokalemia, hypocalcemia, and hypophosphatemia can impair muscle contraction

  • Alveolar-arterial oxygen difference ([A-a]DO2): In children, (A-a)DO2 is normally 5-10

  • PaO2/ fractional concentration of inspired oxygen (FiO2): Indicates gas exchange

  • Oxygen index: (PaO2 x FiO2/mean airway pressure) x 100

  • Dead-space volume to tidal gas volume (VD/VT)

  • Intrapulmonary shunt fraction (Qs/Qt)

Imaging studies

Common radiographic findings associated with respiratory failure include the following:

  • Focal or diffuse pulmonary disease (eg, pneumonia, acute respiratory distress syndrome [ARDS])

  • Bilateral hyperinflation (eg, asthma)

  • Asymmetrical lung expansion suggesting a bronchial obstruction

  • Pleural effusion

  • Cardiomegaly

Bronchoalveolar lavage and lung biopsy

Bronchoalveolar lavage (BAL) is performed to identify a specific infectious pulmonary pathogen; it can also be used to isolate lipid-laden macrophages (suggestive of recurrent aspiration) or pulmonary hemorrhage.

Lung biopsy may be indicated if BAL does not reveal a pathogen and is also helpful in the diagnosis of sarcoidosis and other granulomatous conditions.

See Workup for more detail.

Management

For partial upper-airway obstruction (eg, from anesthesia or acute tonsillitis), place a nasopharyngeal airway to provide a passageway for air. An oropharyngeal airway can be used temporarily in the unconscious patient.

For extrathoracic airway obstruction, as in croup, the following measures may be helpful:

  • Inspired humidity: To liquefy secretions

  • Heliox (helium and oxygen gas mixture): To decrease the work of breathing

  • Racemic epinephrine 2.25% (an aerosolized vasoconstrictor)

  • Systemic corticosteroids: To decrease airway edema

  • Nebulized hypertonic (3%) saline

Lung and respiratory pump support

  • Oxygen therapy: Supplemental oxygen is the initial treatment for hypoxemia

  • Humidified high-flow nasal cannula therapy (HHFNC): May be effective in the treatment of some neonatal respiratory conditions

  • Continuous positive airway pressure (CPAP): May be indicated if lung disease results in severe oxygenation abnormalities

  • Noninvasive positive-pressure ventilation (NPPV): To decrease the work of breathing and provide adequate gas exchange

  • Conventional mechanical ventilation: For acute hypercapnia and severe hypoxemia

  • Inverse ratio ventilation: A nonphysiologic pattern for breathing

  • Airway pressure release ventilation (APRV): A form of inverse-ratio ventilation that allows the patient to breathe spontaneously throughout the ventilatory cycle

  • High-frequency oscillatory ventilation (HFOV): Improves the occurrence and treatment of air-leak syndromes associated with neonatal and pediatric acute lung injury; research suggests, however, that it may lead to poorer outcomes than conventional mechanical ventilation in pediatric acute respiratory failure

Adjunctive therapies for severe hypoxemia

  • Prone positioning: Reduces compliance of the thoracoabdominal cage by impeding the compliant rib cage

  • Inhaled nitric oxide (NO): Potential benefit of NO is to improve ventilation-to-perfusion matching by enhancing pulmonary blood flow to well-ventilated parts of the lung

  • Exogenous surfactant: Improves respiratory mechanics and oxygenation in neonatal respiratory distress syndrome (RDS)

  • Extracorporeal life support (ECLS): Therapy in which blood is removed from the patient, passed through an artificial membrane where gas exchange occurs, and returned to the body by either the arterial (venoarterial [VA]) or venous (venovenous [VV]) system

See Treatment and Medication for more detail.

Background

Pediatric respiratory failure develops when the rate of gas exchange between the atmosphere and blood is unable to match the body's metabolic demands. It is diagnosed when the patient’s respiratory system loses the ability to provide sufficient oxygen to the blood, and hypoxemia develops, or when the patient is unable to adequately ventilate, and hypercarbia and hypoxemia develop.

Management of acute respiratory failure begins with supporting the patient, followed by determining and treating the underlying etiology. While supporting the respiratory system and ensuring adequate gas exchange in the blood, the clinician should initiate an intervention specifically defined to correct the underlying condition. (See Treatment.)

For patient education information, see the Lung Disease & Respiratory Health Center, as well as Acute Respiratory Distress Syndrome (ARDS).

Pathophysiology

Hypoxemia, defined as a decreased level of oxygen in the blood, is caused by one of the following abnormalities:

  • Mismatch between alveolar ventilation (V) and pulmonary perfusion (Q)

  • Intrapulmonary shunt

  • Hypoventilation

  • Abnormal diffusion of gases at the alveolar-capillary interface

  • Reduction in inspired oxygen concentration

  • Increased venous desaturation with cardiac dysfunction plus one or more of the above 5 factors

Hypoxemia is to be distinguished from hypoxia, defined as a decreased level of oxygen in the tissues. These 2 conditions may be closely related and may or may not coexist, but they are not synonymous.

Ventilation-perfusion mismatch, intrapulmonary shunt, and hypoventilation

The 3 most important abnormalities in gas exchange that lead to respiratory failure are V/Q mismatch, intrapulmonary shunt, and hypoventilation.

The V/Q ratio determines the adequacy of gas exchange in the lung. When alveolar ventilation matches pulmonary blood flow, CO2 is eliminated and the blood becomes fully saturated with oxygen. In the normal lung, gravitational forces affect the V/Q ratio. When a person stands, the V/Q is greater than 1 at the apex of the lung (ventilation exceeds perfusion) and less than 1 at the base (less ventilation with more perfusion). In the overall healthy lung, the V/Q ratio is assumed to be ideal and equals 1.

A mismatch between ventilation and perfusion is the most common cause of hypoxemia. When the V/Q ratio is less than 1 throughout the lung, arterial hypoxemia results. As V/Q mismatch worsens, the minute ventilation increases producing either a low or normal arterial partial pressure of CO2 (PaCO2). The hypoxemia caused by low V/Q areas is responsive to supplemental oxygen administration. The more severe the V/Q imbalance, the higher the concentration of inspired oxygen is needed to raise the arterial partial pressure of oxygen (PaO2).

In the extreme case when the V/Q ratio equals 0, pulmonary blood flow does not participate in gas exchange because the perfused lung unit receives no ventilation (V=0). This condition is intrapulmonary shunting and is calculated by comparing the oxygen contents in arterial blood, mixed venous blood, and pulmonary capillary blood (see Workup).

In healthy people, the percentage of intrapulmonary shunt is less than 10%. When the intrapulmonary shunt is greater than 30%, resultant hypoxemia does not improve with supplemental oxygenation because the shunted blood does not come in contact with the high oxygen content in the alveoli. Instead, treatment consists of recruiting and maximizing lung volume with positive pressure. PaO2 continues to fall proportionately as the shunt increases.

In contrast, PaCO2 remains constant because of a compensatory increase in minute ventilation until the shunt fraction exceeds 50%. The protective reflex that reduces the degree of intrapulmonary shunting is hypoxic pulmonary vasoconstriction (HPV); alveolar hypoxia leads to vasoconstriction of the perfusing vessel. This partially corrects the regional V/Q mismatch by improving PaO2 at the expense of increasing pulmonary vascular resistance.

When ventilation is in excess of capillary blood flow, the V/Q ratio is greater than 1. At the extreme, areas of ventilated lung receive no perfusion, and the V/Q ratio approaches infinity (Q=0). This extreme condition is referred to as alveolar dead-space ventilation. In addition to alveolar dead space, anatomic dead space represents the volume of air in conducting airways that cannot participate in gas exchange.

Combined, the alveolar and anatomic dead-space volumes are referred to as physiologic dead space, which normally accounts for 30% of total ventilation. Increased dead-space ventilation results in hypoxemia and hypercapnia. This increase can be caused by decreased pulmonary perfusion due to hypotension, pulmonary embolus, or alveolar overdistention during mechanical ventilation. The ratio of dead-space to tidal-gas volume can be calculated on the basis of the difference between CO2 in arterial blood and in exhaled gas (see Workup).

Under steady-state conditions, PaCO2 is directly proportional to CO2 production (VCO2) and inversely proportional to alveolar ventilation (VA), as follows: PaCO2 = VCO2 X (k/VA), where k is a constant = 0.863.

Therefore, when VA decreases or VCO2 increases, PaCO2 increases. With alveolar hypoventilation, hypoxemia is predicted by using the alveolar gas equation, but the alveolar-arterial gradient remains normal (see Workup).

Another way to approach respiratory failure is based on 2 patterns of blood-gas abnormalities. Type I respiratory failure results from poor matching of pulmonary ventilation to perfusion; this leads to noncardiac mixing of venous blood with arterial blood. As a result, type I respiratory failure is characterized by arterial hypoxemia with normal or low arterial CO2.

Type II respiratory failure results from inadequate alveolar ventilation in relation to physiologic needs and is characterized by arterial hypercarbia and hypoxemia. Type II respiratory failure occurs when a disease or injury imposes a load on a child's respiratory system that is greater than the power available to do the respiratory work. In this scenario, the hypoxemia is proportional to the hypercarbia.

A wide array of diseases can cause respiratory failure. Therefore, the physician must identify the affected area in the respiratory system that contributes to the respiratory failure. Identification can be achieved by dividing the respiratory system into 3 anatomic parts: (1) the extrathoracic airway, (2) the lungs responsible for gas exchange, and (3) the respiratory pump that ventilates the lung and that includes the nervous system, thorax, and respiratory muscles.

In general, diseases that affect the anatomic components of the lung result in regions of low or absent V/Q ratios, initially leading to type I (or hypoxemic) respiratory failure. In contrast, diseases of the extrathoracic airway and respiratory pump result in a respiratory power-load imbalance and type II respiratory failure. Hypercarbia due to alveolar hypoventilation is the hallmark of diseases involving the respiratory pump.

Pediatric considerations

The frequency of acute respiratory failure is higher in infants and young children than in adults, for several reasons. This difference can be explained by defining anatomic compartments and their developmental differences in pediatric patients that influence susceptibility to acute respiratory failure. Neonates present a unique susceptibility to respiratory failure, both resulting from and/or complicated by issues related to prematurity and transition from intrauterine to extrauterine life.

Extrathoracic airway differences

The area extending from the nose through the nasopharynx, oropharynx, and larynx to the subglottic region of the trachea constitutes the extrathoracic airway. This area differs in pediatric versus adult patients in 8 respects, as follows:

  1. Neonates and infants are obligate nasal breathers until the age of 2-6 months because of the proximity of the epiglottis to the nasopharynx. Nasal congestion can lead to clinically significant distress in this age group.

  2. The airway is small; this is one of the primary differences in infants and children younger than 8 years compared with older patients.

  3. Infants and young children have a large tongue that fills a small oropharynx.

  4. Infants and young children have a cephalic larynx. The larynx is opposite vertebrae C3-4 in children versus C6-7 in adults.

  5. The epiglottis is larger and more horizontal to the pharyngeal wall in children than in adults. The cephalic larynx and large epiglottis can make laryngoscopy challenging.

  6. Infants and young children have a narrow subglottic area. In children, the subglottic area is cone shaped, with the narrowest area at the cricoid ring. A small amount of subglottic edema can lead to clinically significant narrowing, increased airway resistance, and increased work of breathing. Adolescents and adults have a cylindrical airway that is narrowest at the glottic opening.

  7. In slightly older children, adenoidal and tonsillar lymphoid tissue is prominent and can contribute to airway obstruction.

  8. Uncorrected congenital anatomic abnormalities (eg, cleft palate, Pierre Robin sequence) or acquired abnormalities (eg, subglottic stenosis, laryngomalacia/tracheomalacia) may cause inspiratory obstruction.

Intrathoracic airway differences

The intrathoracic airways and lung include the conducting airways and alveoli, the interstitia, the pleura, the lung lymphatics, and the pulmonary circulation. There are 6 noteworthy differences between children and adults in this area, as follows:

  1. Infants and young children have fewer alveoli than do adults. The number dramatically increases during childhood, from approximately 20 million at birth to 300 million by 8 years of age. Therefore, infants and young children have a relatively small area for gas exchange.

  2. The alveolus is small. Alveolar size increases from 150-180 to 250-300 µm during childhood.

  3. Collateral ventilation is not fully developed; therefore, atelectasis is more common in children than in adults. During childhood, anatomic channels form to provide collateral ventilation to alveoli. These pathways are between adjacent alveoli (pores of Kohn), bronchiole and alveoli (Lambert channel), and adjacent bronchioles. This important feature allows alveoli to participate in gas exchange even in the presence of an obstructed distal airway.

  4. Smaller intrathoracic airways are more easily obstructed than larger ones. With age, the airways enlarge in diameter and length.

  5. Infants and young children have relatively little cartilaginous support of the airways. As cartilaginous support increases, dynamic compression during high expiratory flow rates is prevented.

  6. Residual alveolar damage from chronic lung disease of prematurity or bronchopulmonary dysplasia decreases pulmonary compliance.

Respiratory pump differences

The respiratory pump includes the nervous system with central control (ie, cerebrum, brainstem, spinal cord, peripheral nerves), respiratory muscles, and chest wall. The following 5 features mark the difference between the pediatric and adult population:

  1. The respiratory center is immature in infants and young children and leads to irregular respirations and an increased risk of apnea.

  2. The ribs are horizontally oriented. During inspiration, a decreased volume is displaced, and the capacity to increase tidal volume is limited compared with that in older individuals.

  3. The small surface area for the interaction between the diaphragm and thorax limits displacing volume in the vertical direction.

  4. The musculature is not fully developed. The slow-twitch fatigue-resistant muscle fibers in the infant are underdeveloped.

  5. The soft compliant chest wall provides little opposition to the deflating tendency of the lungs. This leads to a lower functional residual capacity in pediatric patients than in adults, a volume that approaches the pediatric alveolus critical closing volume.

Etiology

The most common reasons for respiratory failure in the pediatric population can be divided by anatomic compartments, as follows.

Acquired extrathoracic airway causes include the following:

  • Infections (eg, retropharyngeal abscess, Ludwig angina, laryngotracheobronchitis, bacterial tracheitis, peritonsillar abscess)

  • Trauma (eg, postextubation croup, thermal burns, foreign-body aspiration)

  • Other (eg, hypertrophic tonsils and adenoid)

Congenital extrathoracic airway causes include the following:

  • Subglottic stenosis

  • Subglottic web or cyst

  • Laryngomalacia

  • Tracheomalacia

  • Vascular ring

  • Cystic hygroma

  • Craniofacial anomalies

Intrathoracic airway and lung causes include the following:

  • Acute respiratory distress syndrome (ARDS)

  • Asthma

  • Aspiration

  • Bronchiolitis

  • Bronchomalacia

  • Left-sided valvular abnormalities

  • Pulmonary contusion

  • Near drowning

  • Pneumonia

  • Pulmonary edema

  • Pulmonary embolus

  • Sepsis

Respiratory pump causes include the following:

  • Diaphragm eventration

  • Diaphragmatic hernia

  • Flail chest

  • Kyphoscoliosis

  • Duchenne muscular dystrophy

  • Guillain-Barré syndrome

  • Infant botulism

  • Myasthenia gravis

  • Spinal cord trauma

  • Spinal muscular atrophy (SMA)

Central control causes include the following:

  • CNS infection

  • Drug overdose

  • Sleep apnea

  • Stroke

  • Traumatic brain injury

Prognosis

The prognosis depends on the underlying etiology leading to acute respiratory failure. It can be good when the respiratory failure is an acute event that is not associated with prolonged hypoxemia (eg, in the case of a seizure or intoxication). It may be fair to poor when a new process is associated with chronic respiratory failure secondary to a neuromuscular disease or thoracic deformity or in the case of warm hypoxia exceeding 10-20 minutes. This may herald the need for long-term mechanical ventilation.

The prognosis can vary when respiratory failure is associated with a chronic disease with acute exacerbations. Acute respiratory failure remains an important cause of morbidity and mortality in children. Cardiac arrests in children frequently result from respiratory failure. In 2014, data from the National Center for Health Statistics listed respiratory illnesses as one of the top 10 causes of pediatric mortality.[1] Respiratory failure may be the sign of an irreversible progressive disease that leads to death (eg, idiopathic pulmonary hypertension).

 

Presentation

History

Consideration of the questions that follow can help guide the history in a patient with possible respiratory failure.

Does the patient have factors that increase the risk for respiratory failure? Factors may include any of the following:

  • Young age

  • Premature birth

  • Immunodeficiency

  • Chronic pulmonary, cardiac, or neuromuscular disease (eg, cystic fibrosis, bronchopulmonary dysplasia, unrepaired congenital heart disease, spinal muscular atrophy [SMA])

  • Anatomic abnormalities

Does the patient have a cough, rhinorrhea, or other symptoms of an upper respiratory tract infection? These manifestations may help in defining an etiology.

Does the patient have a fever or signs of sepsis? Several infections can lead to respiratory failure because of a systemic inflammatory response, pulmonary edema, or acute respiratory distress syndrome (ARDS) or because of a power-load imbalance secondary to increased oxygen consumption. Epiglottitis from Haemophilus influenzae infection, although decreased in recent years owing to widespread immunization, is a classic cause of obstructive respiratory failure in infants and children.

How long have the symptoms been present? The natural course of a respiratory illness must be considered. Respiratory syncytial virus (RSV) infections, for example, frequently worsen over the initial 3-5 days before improvement occurs.

Does the patient have any pain? Pain can suggest pleuritis or foreign-body aspiration.

Does the patient have a possible or known exposure to sedatives (eg, benzodiazepines, tricyclic antidepressants, narcotics) or has he or she recently undergone a procedure that used general anesthesia? This could suggest hypoventilation.

Does the patient have symptoms of neuromuscular weakness or paralysis? What is the distribution of weakness and duration of symptoms to narrow the differential diagnosis? Bulbar dysfunction suggests myasthenia gravis. Distal weakness that progresses upward suggests Guillain-Barré syndrome. Apnea associated with a traumatic injury suggests a cervical spinal cord injury.

Does the patient have a history suggestive of a stroke or seizure?

Does the patient have a history of headaches? With chronic hypercapnia, headaches typically occur at nighttime or upon the patient's awakening in the morning.

Physical Examination

During the physical examination, the clinician should avoid interfering with the patient's mechanisms for compensation. Children often find the most advantageous position for breathing, which can be a helpful diagnostic clue for the astute clinician.

Children with respiratory distress commonly sit up and lean forward to improve leverage for the accessory muscles and to allow for easy diaphragmatic movement. Children with epiglottitis sit upright with their necks extended and heads forward while drooling and breathing through their mouths. Making a child lie down or making him or her cry during the simplest examination can precipitate acute respiratory failure.

The clinician should observe whether the patient appears well or sick, and should look for central or peripheral cyanosis.

The respiratory rate and quality can provide diagnostic information, and they should be assessed with attention to age-specific norms for each particular patient. Bradypnea is most often observed in central control abnormalities. Slow and large tidal volume breaths also minimize turbulence and resistance in significant extrathoracic airway obstruction (eg, epiglottitis). The fast and shallow breathing of tachypnea is most efficient in intrathoracic airway obstruction. It decreases dynamic compliance of the lung.

Auscultation provides information about the symmetry and quality of air movement. Evaluate the patient for stridor (an inspiratory sound), wheezing (an expiratory sound), crackles, and decreased breath sounds (eg, alveolar consolidation, pleural effusion).

Grunting is an expiratory sound made by infants as they exhale against a closed glottis. It is an attempt to increase functional residual capacity and lung volume. This is done in order to raise functional residual capacity above the critical closing volume and to avoid alveolar collapse. This physical finding represents impending respiratory failure and should not be overlooked.

Assess for accessory muscle use and nasal flaring. Suprasternal and intercostal retractions are present when high negative pleural pressures are required to overcome airway obstruction or stiff lungs.

Evaluate for paradoxical movement of the chest wall. In the presence of abnormalities of the pulmonary pump, paradoxical chest-wall movement occurs because of instability of the chest wall associated with absent intercostal muscle use. As the diaphragm contracts and pushes abdominal contents out, the chest wall retracts inward instead of expanding normally. Termed abdominal breathing, this, however, may be a normal compensatory pattern for a very young infant with chronic lung disease or decreased chest wall compliance.

Tachycardia and hypertension may occur secondary to increased circulatory catecholamine levels. A gallop is suggestive of myocardial dysfunction leading to respiratory failure. Age-specific bradycardia associated with decreased or shallow breathing and desaturations noted via pulse oximeter is ominous and indicates the need for emergent positive-pressure ventilation.

Peripheral vasoconstriction may develop secondary to respiratory acidosis and/or hypoxia.

Patients may be lethargic, irritable, anxious, or unable to concentrate. The inability to breathe comfortably creates anxiety, and superimposed hypoxemia and hypercapnia accentuates any restlessness and agitation. Increased agitation may indicate a general worsening of the patient's condition.

 

DDx

Diagnostic Considerations

Problems to be considered in the differential diagnosis of pediatric respiratory failure include the following:

  • Guillain-Barré syndrome

  • Ludwig angina

  • Neuromuscular disorders (eg, Duchenne muscular dystrophy or spinal muscular atrophy [SMA] type 1)

  • Pulmonary embolus

  • Spinal cord injury

  • Tracheal foreign bodies

  • Transverse myelitis, cervical or high thoracic

  • Vascular slings

Differential Diagnoses

 

Workup

Approach Considerations

Arterial blood gas (ABG) measurement can be used to define acute respiratory failure. Arbitrary definitions include a partial pressure of CO2 (PaCO2) greater than 50 mm Hg, a partial pressure of oxygen (PaO2) less than 60 mm Hg, or arterial oxygen saturation less than 90%. An elevated serum bicarbonate level suggests metabolic compensation for chronic hypercapnia.

A complete blood count (CBC) may be helpful. Polycythemia suggests chronic hypoxemia.

Electrolyte abnormalities can contribute to weakness; hypokalemia, hypocalcemia, and hypophosphatemia can impair muscle contraction.

Calculate the alveolar-arterial oxygen difference ([A-a]DO2), which is the difference between the alveolar PAO2 and the arterial PaO2. This value is an index of the efficiency of gas exchange by the lungs.

The alveolar gas equation is used to calculate the PAO2 on the basis of the relationship between the pressure of oxygen in inspired gas (PiO2), the PaCO2, and the respiratory quotient (RQ), as follows: PAO2 = FiO2 (Pb - PH 2O) - (PaCO2/RQ).

PiO2 is a function of the fractional concentration of inspired oxygen (FiO2), the barometric pressure (Pb), and the partial pressure of water vapor (PH 2O) in humidified air.

RQ is the ratio of the volume of carbon dioxide expired to the volume of oxygen consumed by an organism. The body normally produces approximately 200 mL of carbon dioxide per minute and consumes approximately 250 mL of oxygen per minute; therefore, RQ is 0.8. Different fuel sources produce different RQ values: the RQ for carbohydrates is 1; protein is 0.8; and fat is 0.7.

In children, (A-a)DO2 is normally 5-10 and reflects venous admixture from anatomic right-to-left shunts, which include the bronchial circulation, thebesian veins, and small arteriovenous anastomoses in the lung.

The PaO2/FiO2 ratio is a commonly used indicator of gas exchange. A PaO2/FiO2 less than 200 is correlated with a shunt fraction greater than 20%. For ventilated patients, a similar calculation is called the oxygen index, calculated by (PaO2 x FiO2/mean airway pressure) x 100. These numbers are used to quickly communicate the severity of respiratory failure and can provide some diagnostic and therapeutic guidance (eg, when to start inhaled nitric oxide).

Imaging studies may include plain radiography or computed tomography (CT), or magnetic resonance imaging (MRI) scans. Fluoroscopy is valuable to evaluate the movement of the diaphragms and dynamic obstructive lesions of both the extrathoracic and intrathoracic airway. Ventilation/perfusion (V/Q) scanning can predict a probability of V/Q mismatch secondary to a pulmonary embolism.

Imaging Studies

Radiography

Lateral and anteroposterior (AP) radiographs of the neck can reveal a radiopaque foreign body or soft-tissue structures encroaching on the lumen of the airway, such as in acute epiglottitis.

Chest radiographs may yield helpful findings (see examples in the images below).

Bilateral airspace infiltrates on chest radiograph Bilateral airspace infiltrates on chest radiograph film secondary to acute respiratory distress syndrome that resulted in respiratory failure.
Extensive left-lung pneumonia caused respiratory f Extensive left-lung pneumonia caused respiratory failure; the mechanism of hypoxia is intrapulmonary shunting.

Evaluate for abnormalities that require immediate intervention (eg, malpositioned endotracheal tube, pneumothorax).

Common findings associated with respiratory failure include the following:

  • Focal or diffuse pulmonary disease (eg, pneumonia, ARDS)

  • Bilateral hyperinflation (eg, asthma)

  • Asymmetric lung expansion suggesting a bronchial obstruction

  • Pleural effusion

  • Cardiomegaly

If hypoxemia is present but the chest radiograph is clear, this finding could suggest cyanotic congenital heart disease, pulmonary hypertension, or pulmonary emboli.

CT and MRI

Chest CT scanning can be performed when sophisticated diagnostic images are needed. It can further define radiopacities due to vascular, pleural, interstitial, or airway lesions.

Airway CT scanning, MRI, and/or angiography can be used to differentiate deep-tissue structures, bone lesions, and vascular abnormalities.

Other Pulmonary Function Tests

Useful information may be provided by determination of dead-space volume to tidal gas volume (VD/VT) and determination of the intrapulmonary shunt fraction (Qs/Qt).

Determination of dead-space volume to tidal gas volume

VD/VT is based on the difference between PaCO2 and the CO2 in exhaled gas (PeCO2). PeCO2 is measured by collecting expired gas in a large collection bag and using an infrared CO2 analyzer to measure the PCO2 in a sample of gas.

In a normal lung, the capillary blood equilibrates fully with alveolar gas; therefore, the PeCO2 approximates the PaCO2. As VD/VT increases, the PeCO2 falls below PaCO2.

Reference range VD/VT is approximately 0.30.

VD/VT = (PaCO2 - PeCO2)/PaCO2

Determination of the intrapulmonary shunt fraction

Qs/Qt is the ratio of shunted flow (Qs) to the total flow or cardiac output (Qt). It is derived by the relationship between the oxygen content in arterial blood (CaO2), mixed venous blood (CvO2), and pulmonary capillary blood (CcO2) while breathing FiO2 that equals 1.

Arterial oxygen content (in mL O2/dL) = [1.34 mL O2/g hemoglobin × hemoglobin (in g/dL) × SpO2] + [PaO2 (in mm Hg) × 0.003 mL O2/dL/mm Hg].

Directly measuring pulmonary capillary blood (CcO2) is difficult; therefore, CcO2 is assumed to be 100% when FiO2 equals 1.

The normal intrapulmonary shunt is less than 10%.

Qs/Qt = (CcO2 - CaO2)/(CcO2 - CvO2)

Bronchoalveolar Lavage and Lung Biopsy

Bronchoalveolar lavage (BAL) is performed to identify a specific infectious pulmonary pathogen; bacterial, viral, and acid-fast bacillus (AFB) cultures and silver stains can be performed. BAL can also be performed to isolate lipid-laden macrophages (suggestive of recurrent aspiration) or pulmonary hemorrhage.

In an intubated patient, samples can be obtained blindly or bronchoscopically.

BAL is indicated in critically ill children to guide antimicrobial therapy and in children whose conditions have deteriorated during therapy.

Lung biopsy may be indicated if BAL does not reveal a pathogen, especially in immunocompromised hosts; it can identify Aspergillus species or Pneumocystis jiroveci. Lung biopsy is also helpful in the diagnosis of sarcoidosis and other granulomatous conditions. However, the value of confirming a diagnosis in these vulnerable patients must be weighed against the risks of an invasive procedure. A recent retrospective analysis of 50 immunocompromised children undergoing surgical lung biopsy suggested that whereas therapy was altered in 50% of patients, 12% experienced major postoperative morbidities and 2 patients died.[2]

Other Tests

Electromyography (EMG) or nerve conduction testing can help determine the etiology for neuromuscular weakness leading to respiratory pump failure.

Fiberoptic and rigid bronchoscopy can be performed to assess large and small airways for anatomic abnormalities or foreign bodies.

Nasal airflow tracings coupled with chest-movement recordings (pneumograms) have a specific role in identifying sleep-associated extrathoracic airway obstruction and respiratory control abnormalities.

Thoracentesis is used in patients with pleural effusions, to check the cell count and protein level to determine whether pleural fluid is an exudate or transudate. Other pleural fluid studies include measurement of triglycerides, to determine whether the effusion is chylous, and bacterial and acid-fast bacterial (AFB) cultures. Cytology is used to evaluate for malignant effusions.

Test of respiratory mechanics and lung-volume measurements are most beneficial in following the progression of disease and the effects of treatment over time. Many infants and children cannot cooperate with traditional pulmonary function measurements. Many contemporary pediatric ventilators incorporate sophisticated sensors and software that measure inhaled and exhaled breaths and can display pulmonary flow loops and other pulmonary parametrics. This provides valuable information regarding real-time, as well as trended, pulmonary dynamics.

 

Treatment

Approach Considerations

Management of acute respiratory failure begins with a determination of the underlying etiology. While supporting the respiratory system and ensuring adequate oxygen delivery to the tissues, initiate an intervention specifically defined to correct the underlying condition. For example, a patient with status asthmaticus is given supplemental oxygen to treat hypoxemia, but corticosteroids and beta-agonist drugs are also given to treat the underlying pathology.

See the following Medscape Drugs & Diseases articles for specific treatment: Pediatric Acute Respiratory Distress Syndrome, Pediatric Pneumonia, Pediatric Asthma, and Pediatric Status Asthmaticus.

Extrathoracic airway support

For partial upper-airway obstruction (eg, from anesthesia or acute tonsillitis), place a nasopharyngeal airway to provide a passageway for air.[3] An oropharyngeal airway can be used temporarily in the unconscious patient.

For extrathoracic airway obstruction, such as croup, the following measures may be helpful:

  • Inspired humidity to liquefy secretions

  • Heliox (helium and oxygen gas mixture) to decrease work of breathing

  • Racemic epinephrine 2.25%, an aerosolized vasoconstrictor

  • Systemic corticosteroids to decrease airway edema

  • Nebulized hypertonic (3%) saline

  • Nebulized isotonic (0.9%) saline

Heliox has a helium concentration of 60-80% and thus has a density lower than that of air; it improves breathing by reducing turbulent airflow through a narrowed area. A limiting factor in the use of Heliox is that it typically contains oxygen in the same concentration as room air, and some patients may require higher concentrations of oxygen.

Consultations

Consultations may be indicated with the following:

  • Neurologist for neuromuscular weakness evaluation

  • Cardiologist if left-sided valvar obstruction or cardiomyopathy is suspected

  • Pulmonologist for chronic pulmonary diseases

  • Otorhinolaryngologist for evaluation of foreign-body aspiration or anatomic abnormality

Tracheal Intubation

Endotracheal intubation is occasionally needed to maintain airway patency in certain cases (eg, epiglottitis, thermal burns to the airway, severe croup). In general, uncuffed tubes are used in children younger than 8 years because the subglottic trachea surrounded by the cricoid cartilage is the narrowest part of the pediatric airway.

In neonates and infants younger than 6 months, an endotracheal tube with an inner diameter (ID) of 3.5-4 mm is appropriate. In infants aged 6-12 months, a tube with a 4-4.5 mm ID is appropriate. Weight is the traditional guide to determine appropriate endotracheal tube size in infants and children, and many emergency departments have a color-coded emergency equipment cart organized by weight for easy access. A useful bedside or field guideline for appropriate endotracheal tube size is approximately the size of the patient’s fifth finger.

In children older than 1 year, the following formula can be used: Tube size (ID in millimeters) = (age in years + 16)/4

The mnemonic MSOAPP can be used to remember the preparation essential for a safe tracheal intubation procedure, as follows:

  • M - Monitors (heart rate, blood pressure, pulse oximetry, capnography for CO2 detection)

  • S - Suction and catheters

  • O - Oxygenation with a bag-valve mask

  • A - Apparatus (laryngoscope, endotracheal tubes appropriate for the patient's age and a half-size smaller and larger, stylets, oral airways)

  • P - Pharmacy (medications for amnesia and paralysis)

  • P = People (respiratory therapist, nurse, a skilled set of hands)

In adults, confirming proper sizing is accomplished by allowing the breathing circuit pressure to rise until air leaking around the tube can be auscultated, ideally approximately 15-18 cm water; the endotracheal tube cuff is then inflated. In infants and children, there is no cuff, and it is not uncommon to require pressures much higher than 18 cm water to provide adequate ventilatory support. Therefore, it is important to place the proper-diameter endotracheal tube to optimize ventilatory support. Radiographic confirmation should always be obtained, with the distal tip ideally positioned midway between the thoracic inlet and the carina.

Lung and Respiratory Pump Support

Oxygen therapy

The initial treatment for hypoxemia is to provide supplemental oxygen. High-flow (>15 L/min) oxygen delivery systems include a Venturi-type device that places an adjustable aperture lateral to the stream of oxygen. Oxygen is mixed with entrained room air, and the amount of air is adjusted by varying the aperture size. The oxygen hoods and tents also supply high gas flows.

Low-flow (< 6 L/min) oxygen delivery systems include the nasal cannula and simple face mask.

Humidified high-flow nasal cannula therapy

Although no single universally accepted definition is available for what constitutes humidified high-flow nasal cannula (HHFNC) therapy in neonates, a widely used and reasonable definition is optimally warmed (body temperature) and humidified respiratory gases delivered by nasal cannula at flow rates of 2-8 L/min.[4]

In 2004, the US Food and Drug Administration (FDA) approved a device specifically for the provision of HHFNC in neonates: Vapotherm 2000i (Vapotherm, Inc, Stevensville, MD). This devices delivered molecular vapor with 95-100% relative humidity at body temperature through nasal cannula at flow rates between 5-40 L/min.

In August 2005, the Centers for Disease Control and Prevention (CDC) was notified of a Ralstonia species outbreak among pediatric patients receiving supplemental oxygen therapy with the Vapotherm 2000i. It was recalled from the market but has subsequently been reintroduced.[5]

Following the withdrawal of Vapotherm from the market, many individual neonatal and pediatric centers put together their own systems for delivery of HHFNC using the basic components of a humidifier, respiratory circuit, adapter, and nasal cannula.

Limited evidence is available to support the specific role, efficacy, and safety of HHFNC. The available evidence suggests that HHFNC provides inconsistent and relatively unpredictable positive airway pressure but may be effective in the treatment of some neonatal respiratory conditions while being more user-friendly for caregivers and better tolerated by infants and toddlers than conventional CPAP.[6, 7] A recent trial assessing noninferiority of HHFNC (5-6 L/min) to nasal continuous positive airway pressure (CPAP) (7 cm water) in preterm infants after extubation failed to demonstrate a difference in the 2 modalities. Nasal trauma occurred less frequently in the HHFNC group.[8]

Continuous positive airway pressure

CPAP may be indicated if lung disease results in severe oxygenation abnormalities such that an FiO2 greater than 0.3 is needed to maintain a PaO2 greater than 60 mm Hg.

CPAP in pressures from 3-10 cm water is applied to increase lung volume and may redistribute pulmonary edema fluid from the alveoli to the interstitium.

CPAP enhances ventilation to areas with low V/Q ratios and improves respiratory mechanics. Furthermore, CPAP may be of benefit in locales where invasive ventilatory support is not available. A recent study of the effectiveness of CPAP in children aged 3 months to 5 years presenting with acute respiratory distress in Ghana was stopped after enrolling 70 patients (35 patients per arm), owing to the statistical superiority of CPAP.[9]

If a high concentration of FiO2 is needed and if the patient does not tolerate even short periods of discontinued airway pressure, positive-pressure ventilation should be administered.

Noninvasive positive-pressure ventilation (NPPV)

Noninvasive positive-pressure ventilation (NPPV) refers to assisted ventilation provided with nasal prongs or a face mask instead of an endotracheal or tracheostomy tube. This therapy can be administered to decrease the work of breathing and to provide adequate gas exchange.

NPPV can be given by using a volume ventilator, a pressure-controlled ventilator, or a device for bilevel positive airway pressure (BIPAP or bilevel ventilator) (see the image below).

The RAM cannula, developed by a clinician at the Children’s Hospital of Los Angeles, provides the comfort and ease of a nasal cannula and, when attached to a ventilator circuit, can deliver true noninvasive positive-pressure ventilation in both the conventional mode and the high-frequency mode. Currently, it is the only device that has this capability.

A Bilevel positive airway pressure support machine A Bilevel positive airway pressure support machine is shown here. This could be used in spontaneous mode or timed mode (backup rate could be set).

Inspiratory pressure support is a ventilator modality in which increased circuited pressure during inspiration boosts the patient's effort. However, the patient's effort, as reflected by sensitive measurement of the circuit gas flow, triggers both the beginning and end of the inspiratory phase of the mechanical cycle.

Potential drawbacks of noninvasive ventilation include inappropriate delay of the start of mechanical ventilation via endotracheal tube.[10] In addition, gastric distention can occur, with possible pulmonary aspiration.

The severity of the patient's disease limits the use of this technique. Prolonged wearing of the facial interface can lead to nasal congestion, facial reddening, eye irritation, or ulceration of the nasal bridge. If periodic relief from the face mask or nasal prongs is unavailable for several days, tracheal intubation is necessary and safer.

Conventional mechanical ventilation

Mechanical ventilation increases minute ventilation and decreases dead space. This approach is the mainstay of treatment for acute hypercapnia and severe hypoxemia. Conventional mechanical ventilation optimizes lung recruitment, increases mean airway pressure and functional residual capacity, and reduces atelectasis between breaths.

A primary strategy for mechanical ventilation should be the avoidance of high peak inspiratory pressures and the optimization of lung recruitment. In adults with ARDS, a strategy to provide low tidal volume (6 mL/kg) with optimized positive end-expiratory pressure (PEEP) offers a substantial survival benefit compared with a strategy for high tidal volume (12 mL/kg).

According to the permissive hypercapnia strategy in ARDS, arterial CO2 is allowed to rise to levels as high as 100 mm Hg while the blood pH is maintained above 7.2 by means of intravenous administration of buffer solutions. This is done to limit inspiratory airway pressure to values below 35 cm water.

PEEP should be applied to a point above the inflection pressure such that alveolar distention is maintained throughout the ventilatory cycle.

Inverse ratio ventilation

During positive pressure ventilation, the inspiratory phase is prolonged in excess of the expiratory phase. This increases mean airway pressure and improves oxygenation during severe acute lung disease. Inverse ratio ventilation is a nonphysiologic pattern for breathing; therefore, these patients are administered heavy sedation and paralysis.

Airway pressure release ventilation (APRV)

Airway pressure release ventilation (APRV) is a relatively new form of inverse-ratio ventilation in which a continuous gas flow circuit is used. This method allows the patient to breathe spontaneously throughout the ventilatory cycle.

In concept, APRV applies a continuous airway pressure (Phigh) identical to that of CPAP to maintain lung volume and promote alveolar recruitment. In addition, a time-cycled release phase lowers the set pressure (Plow) to augment ventilation.

Clinical and experimental studies with APRV demonstrate improvements in gas exchange, cardiac output, and systemic blood flow. Some data suggest reduced use of sedatives and neuromuscular blockers.[11]

High-frequency oscillatory ventilation (HFOV)

High-frequency oscillatory ventilation (HFOV) combines small tidal volumes (smaller than the calculated airway dead space) with frequencies of 15 Hz to minimize the effects of elevated peak and mean airway pressures.

HFOV has proven benefit in improving the occurrence and treatment of air-leak syndromes associated with neonatal and pediatric acute lung injury.

Adjunctive Therapies for Severe Hypoxemia

Prone positioning

Prone positioning reduces compliance of the thoracoabdominal cage by impeding the compliant rib cage. Gases should distribute toward the sternal and anterior diaphragmatic regions that become dependent on prone positioning. Improved homogeneity of ventilation improves oxygenation. This measure may cause a redistribution of blood flow, improving the V/Q match.

Researchers in a multicenter randomized controlled clinical trial concluded that prone positioning did not significantly reduce ventilator-free days, mortality, or time to recovery in pediatric patients with acute lung injury.[12]

Inhaled nitric oxide

Nitric oxide (NO) is an endogenous free radical that mediates smooth muscle relaxation throughout the body. When delivered by means of inhalation, the potential benefit of NO is to improve ventilation to perfusion matching by enhancing pulmonary blood flow to well-ventilated parts of the lung.

This therapy is relatively safe because hemoglobin inactivates it quickly and because does not cause systemic vasodilation leading to hypotension. However, methemoglobin and nitrogen dioxide (NO2) levels should be monitored.

Inhaled NO is being studied for use in type I respiratory failure; in 1999, the FDA approved its use in neonates with hypoxic respiratory failure and evidence of pulmonary hypertension. Research continues on the value of inhaled NO for other pulmonary conditions, such as bronchopulmonary dysplasia, as well as possible roles for other mediators of pulmonary vasodilation, such as sildenafil and bosentan.

Administration of exogenous surfactant

Surfactant is an endogenous complex of lipids and proteins that lines the walls of alveoli and promotes alveolar stability by reducing surface tension. Relative surfactant deficiency and inactivation are variably present as a consequence of many lung diseases.

Exogenous surfactant replacement is of clear benefit to improve respiratory mechanics and oxygenation in the neonatal respiratory distress syndrome (RDS). Its role in severe lung injury in other pediatric populations or adults is still being investigated. Researchers in a multicenter randomized blinded clinical trial concluded that exogenous surfactant replacement in pediatric acute lung injury decreased mortality but that it had no effect on ventilator-free days.[13]

One deterrent to surfactant administration is the need for endotracheal intubation for its delivery. An intriguing pilot study recently completed suggests that exogenous surfactant may be successfully administered via placement of a laryngeal mask airway (LMA), rather than an endotracheal tube.[14]

Complications of mechanical ventilation

In a spontaneously breathing patient with high minute ventilation, care must be taken to maintain that level if tracheal intubation is required. The purpose is to avoid a sudden increase in PaCO2 that could contribute to hemodynamic instability or cardiopulmonary arrest.

Tracheal intubation may lead to upper-airway edema and difficult extubation, especially in patients with chronic illness and a limited baseline pulmonary reserve.

Ventilator-induced lung injury (VILI) may occur secondary to alveoli overdistention (volutrauma). Air-leak syndromes, pneumothorax, or pulmonary interstitial emphysema may occur secondary to elevated inspiratory pressures. Prolonged mechanical ventilation can lead to diaphragmatic atrophy and contractile dysfunction, termed ventilator-induced diaphragmatic dysfunction (VIDD), and VILI from positive pressure ventilation (PPV) (but not negative pressure ventilation [NPV]) may play a role in the development of VIDD. However, a recent study in rats showed no difference in the occurrence of VIDD with PPV versus NPV.[15]

Posthypercapnic alkalosis can occur in patients with chronic hypercapnia if PaCO2 is rapidly reduced with mechanical ventilation. The kidneys have a relatively slow mechanism to correct the bicarbonate excess. The metabolic alkalosis can be treated by replacing chloride or by increasing renal bicarbonate excretion with acetazolamide.

Extracorporeal life support (ECLS)

In extracorporeal life support (ECLS), blood is removed from the patient, passed through an artificial membrane where gas exchange occurs, and is returned to the body by either the arterial (venoarterial [VA]) or venous (venovenous [VV]) system. VV ECLS has become the preferred method for patients of all age groups who do not require cardiac support.

If a patient has moderate-to-severe oxygenation issues, the decision to transfer him or her to a tertiary care center for potential rescue therapy with ECLS should be made within the first 5 days of acute illness. Recent review of neonates included in the Extracorporeal Life Support Organization (ELSO) Registry from 2001-2010 suggests that neonates cannulated for ECLS after the first week of life had lower incidence of CNS hemorrhage but higher mortality than those cannulated earlier.[16]

Data from many studies support the use of ECLS in neonatal respiratory failure when the mortality risk is high. Further studies in pediatric patients are under way. In 2004, the ELSO Registry reported that the number of pediatric respiratory cases was relatively constant (approximately 200 cases per year), with an overall survival rate of 56%.[17] Individual centers have shown varying survival rates. From 2005-2009, Children’s Healthcare of Atlanta (CHA), a recognized center of excellence for pediatric extracorporeal membrane oxygenation (ECMO) in the United States, reported survival rates of 47-75%(see Table 1, below).

Table 1. Survival Statistics from CHA, 2005-2009 [18] (Open Table in a new window)

Year

CHA (US)

International

2005

58%

54%

2006

47%

53%

2007

71%

56%

2008

57%

54%

2009

75%

55%

In 2008, the ELSO Registry report showed a downward trend in the number of respiratory ECLS cases and an upward trend in the number of cardiac cases for all age groups,[19] but this trend reversed in 2009 with the influenza A (H1N1) pandemic, with 73 centers reporting the use of ECMO for H1N1 patients (see Table 2, below). Of 243 patients, 90 were pediatric and 7 were neonates. At the time of the report, mortality was 33.5% (83 patients).[20]

Table 2. 2009 Top 5 Diagnoses for ECMO and Survival Rates [18] (Open Table in a new window)

Diagnosis

CHA (US)

International

Bacterial pneumonia

74%

57%

Viral pneumonia

78%

63%

Aspiration pneumonia

92%

66%

Non-ARDS acute respiratory failure

62%

51%

Other

65%

52%

 

Medication

Medication Summary

The use of medications in the treatment of respiratory failure depends on the underlying disorder. For example, corticosteroids and beta-agonist medications treat an asthma exacerbation, whereas antibiotics treat bacterial pneumonia. Patients with pulmonary edema from myocardial dysfunction improve with diuretics and inotropic support.

Pulmonary Vasodilators

Class Summary

Inhaled nitric oxide (NO) is a pulmonary vasodilator indicated to treat pulmonary hypertension. NO is also being studied for severe hypoxemia in acute respiratory distress syndrome (ARDS).

Nitric oxide, inhaled (INOmax)

NO is produced endogenously from the action of the enzyme NO synthetase on arginine. It relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which then leads to vasodilation. When inhaled, NO decreases pulmonary vascular resistance and improves lung blood flow.

Lung Surfactants

Class Summary

Exogenous surfactant can be helpful in the treatment of airspace disease. After inhalation, surface tension is reduced and alveoli are stabilized, decreasing the work of breathing and increasing lung compliance. These drugs are indicated for the prevention and treatment of neonatal RDS. They are also being investigated for the treatment of hypoxemia secondary to ARDS.

Calfactant (Infasurf)

This is a natural bovine calf lung extract containing phospholipids, fatty acids, and surfactant-associated proteins B (260 mcg/mL) and C (390 mcg/mL). Surfactant is an endogenous complex of lipids and proteins that lines alveolar walls and promotes alveolar stability by reducing surface tension. Relative surfactant deficiency is variably present in many lung diseases.

Poractant alfa (Curosurf)

Poractant alfa lines the alveolar walls and promotes alveolar stability against collapse by reducing surface tension at the air-liquid interface of the alveoli.