Pediatric Respiratory Failure
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.
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)
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.
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)
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
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.
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
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.)
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)
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.
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.
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:
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.
The airway is small; this is one of the primary differences in infants and children younger than 8 years compared with older patients.
Infants and young children have a large tongue that fills a small oropharynx.
Infants and young children have a cephalic larynx. The larynx is opposite vertebrae C3-4 in children versus C6-7 in adults.
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.
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.
In slightly older children, adenoidal and tonsillar lymphoid tissue is prominent and can contribute to airway obstruction.
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:
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.
The alveolus is small. Alveolar size increases from 150-180 to 250-300 µm during childhood.
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.
Smaller intrathoracic airways are more easily obstructed than larger ones. With age, the airways enlarge in diameter and length.
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.
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:
The respiratory center is immature in infants and young children and leads to irregular respirations and an increased risk of apnea.
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.
The small surface area for the interaction between the diaphragm and thorax limits displacing volume in the vertical direction.
The musculature is not fully developed. The slow-twitch fatigue-resistant muscle fibers in the infant are underdeveloped.
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.
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 web or cyst
Intrathoracic airway and lung causes include the following:
Acute respiratory distress syndrome (ARDS)
Left-sided valvular abnormalities
Respiratory pump causes include the following:
Duchenne muscular dystrophy
Spinal cord trauma
Spinal muscular atrophy (SMA)
Central control causes include the following:
Traumatic brain injury
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.  Respiratory failure may be the sign of an irreversible progressive disease that leads to death (eg, idiopathic pulmonary hypertension).
Naiditch JA, Barsness KA, Rothstein DH. The utility of surgical lung biopsy in immunocompromised children. J Pediatr. 2013 Jan. 162(1):133-6.e1. [Medline].
Institute for Clinical Systems Improvement (ICSI). Diagnosis and treatment of respiratory illness in children and adults. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2008 Jan.
de Klerk A. Humidified high-flow nasal cannula: is it the new and improved CPAP?. Adv Neonatal Care. 2008 Apr. 8(2):98-106. [Medline].
Ralstonia associated with Vapotherm oxygen delivery device–United States, 2005. MMWR Morb Mortal Wkly Rep. 2005 Oct 21. 54(41):1052-3. [Medline].
Spence KL, Murphy D, Kilian C, McGonigle R, Kilani RA. High-flow nasal cannula as a device to provide continuous positive airway pressure in infants. J Perinatol. 2007 Dec. 27(12):772-5. [Medline].
Campbell DM, Shah PS, Shah V, Kelly EN. Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants. J Perinatol. 2006 Sep. 26(9):546-9. [Medline].
Manley BJ, Owen LS, Doyle LW, et al. High-flow nasal cannulae in very preterm infants after extubation. N Engl J Med. 2013 Oct 10. 369(15):1425-33. [Medline].
Wilson PT, Morris MC, Biagas KV, Otupiri E, Moresky RT. A randomized clinical trial evaluating nasal continuous positive airway pressure for acute respiratory distress in a developing country. J Pediatr. 2013 May. 162(5):988-92. [Medline].
Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004 Jun 10. 350(24):2452-60. [Medline].
Habashi NM. Other approaches to open-lung ventilation: airway pressure release ventilation. Crit Care Med. 2005 Mar. 33(3 Suppl):S228-40. [Medline].
Curley MA, Hibberd PL, Fineman LD, et al. Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial. JAMA. 2005 Jul 13. 294(2):229-37. [Medline].
Willson DF, Thomas NJ, Markovitz BP, et al. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA. 2005 Jan 26. 293(4):470-6. [Medline]. [Full Text].
Attridge JT, Stewart C, Stukenborg GJ, Kattwinkel J. Administration of rescue surfactant by laryngeal mask airway: lessons from a pilot trial. Am J Perinatol. 2013 Mar. 30(3):201-6. [Medline].
Bruells CS, Smuder AJ, Reiss LK, Hudson MB, Nelson WB, Wiggs MP. Negative pressure ventilation and positive pressure ventilation promote comparable levels of ventilator-induced diaphragmatic dysfunction in rats. Anesthesiology. 2013 Sep. 119(3):652-62. [Medline].
Smith KM, McMullan DM, Bratton SL, Rycus P, Kinsella JP, Brogan TV. Is age at initiation of extracorporeal life support associated with mortality and intraventricular hemorrhage in neonates with respiratory failure?. J Perinatol. 2014 Mar 6. [Medline].
Conrad SA, Rycus PT, Dalton H. Extracorporeal Life Support Registry Report 2004. ASAIO J. 2005 Jan-Feb. 51(1):4-10. [Medline].
Children’s Healthcare of Atlanta. Available at http://www.lchoa.org/childrens-hospital-services/critical-care/ECMO-center/Volumes-and-Outcomes. Accessed: 14 January, 2012.
Haines NM, Rycus PT, Zwischenberger JB, Bartlett RH, Undar A. Extracorporeal Life Support Registry Report 2008: neonatal and pediatric cardiac cases. ASAIO J. 2009 Jan-Feb. 55(1):111-6. [Medline].
Extracorporeal Life Support Organization. H1N1 ECLS Registry, Statistics from the H1N1 Registry (as of May 28, 2010). Available at http://www.elso.med.umich.edu/H1N1Registry.html.
Gadek JE, DeMichele SJ, Karlstad MD, et al. Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med. 1999 Aug. 27(8):1409-20. [Medline].
Singer P, Shapiro H. Enteral omega-3 in acute respiratory distress syndrome. Curr Opin Clin Nutr Metab Care. 2009 Mar. 12(2):123-8. [Medline].
Gupta P, Green JW, Tang X, et al. Comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure. JAMA Pediatr. 2014 Mar. 168(3):243-9. [Medline].
High-Frequency Oscillatory Ventilation Risky in Pediatric Respiratory Failure. Medscape. Jan 24 2014. Available at http://www.medscape.com/viewarticle/819731. Accessed: Feb 4 2014.
Non-ARDS acute respiratory failure
Shelley C Springer, JD, MD, MSc, MBA, FAAP Professor, University of Medicine and Health Sciences, St Kitts, West Indies; Clinical Instructor, Department of Pediatrics, University of Vermont College of Medicine; Clinical Instructor, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health
Shelley C Springer, JD, MD, MSc, MBA, FAAP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Margaret A Priestley, MD Associate Professor of Clinical Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania; Clinical Director, Pediatric Intensive Care Unit, The Children’s Hospital of Philadelphia
Disclosure: Nothing to disclose.
Jimmy W Huh, MD Associate Professor of Anesthesiology, Critical Care and Pediatrics, Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania and Children’s Hospital of Philadelphia
Disclosure: Nothing to disclose.
Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children’s Hospital of Wisconsin
Disclosure: Nothing to disclose.
G Patricia Cantwell, MD Clinical Professor, Department of Pediatrics, Miller School of Medicine, University of Miami; Director of Pediatric Critical Care Medicine, Holtz Children’s Hospital/Jackson Memorial Hospital
G Patricia Cantwell, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.
Barry J Evans, MD Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children’s Medical Center
Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Pediatric Respiratory Failure
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