Acute respiratory failure in children is the inability of the respiratory system to support oxygenation, ventilation, or both. Hypoxic respiratory failure is defined by an arterial partial pressure of oxygen (PaO2) below 60 mm Hg, which typically produces an arterial oxygen saturation of 90%. Ventilation is the elimination of CO2 and is measured by the arterial partial pressure of CO2 (PaCO2). Acute hypercarbic respiratory failure is defined by an acute increase in PaCO2 greater than 50 mm Hg. It is typically associated with a respiratory acidosis pH of <7.35. Venous blood may be sampled in lieu of arterial blood to obtain the venous partial pressure of CO2 (PvCO2); however, it can only be accurately stated that the PaCO2 is no higher than the PvCO2. Therefore, when PvCO2 is <50 mm Hg, acute hypercarbic respiratory failure can be ruled out but a PvCO2 of 55 mm Hg does not guarantee a diagnosis of hypercarbic respiratory failure. PvCO2 is a test that has high sensitivity but poor specificity for diagnosing hypercarbic respiratory failure. PvCO2 should be interpreted carefully based on location of sampling, manner of sampling, and cardiac output.
Acute respiratory failure is a common reason for admission to the pediatric intensive care unit (PICU). The epidemiology is not well described due to inconsistent and heterogeneous diagnostic criteria. In patients with respiratory failure who have underlying pediatric acute respiratory distress syndrome (ARDS), epidemiologic data reveal an annual incidence of 2.3% of PICU admissions, and a mortality rate of 24% to 34%.1,2
Physiology and Pathophysiology
Normal control of breathing is a complex interaction between the vasculature, brain, lungs, and respiratory apparatus. Peripheral chemoreceptors, located in the aortic and carotid bodies, are sensitive to PaO2, PaCO2, and pH. A decrease in PaO2, a decrease in pH or an increase in CO2 results in signaling to increase ventilation. Central chemoreceptors in the brain are sensitive to cerebral spinal fluid (CSF) pH. The blood-brain barrier allows CO2, but not hydrogen ions, to pass freely so the CSF pH is determined by PaCO2. Therefore, the central chemoreceptors can detect small changes in CO2. Input from peripheral and central chemoreceptors is integrated in the brainstem. The pons and medulla generate periodic impulses to trigger breathing. Injury to the brainstem leads to characteristic, abnormal respiratory patterns based on the level of injury.3 The cortex can override this automatic mechanism with voluntary respiratory effort.
The main muscle of inspiration is the diaphragm, which is innervated by the phrenic nerve that originates from spinal nerve roots C3 to C5. Thus, patients with spinal cord injuries at or above this level are at risk for diaphragmatic paralysis and respiratory failure. Phrenic nerve stimulation causes contraction and flattening of the dome-shaped diaphragm. This leads to an increase in intrathoracic volume and consequently a decrease in intrathoracic pressure. A negative pressure gradient is generated between the alveoli and the external environment, resulting in net movement of air to the alveoli. This negative pressure breathing is contrasted to the positive pressure breathing of invasive mechanical ventilation.
Thoracic spinal nerve roots innervate the external intercostal muscles to aid in inspiration by pulling the chest upward and anteriorly. Exhalation is a passive process during quiet breathing due to the elastic recoil of the lungs and chest wall. When exercising or in respiratory distress, exhalation can be an active process assisted by internal intercostal muscles pulling the rib cage inwards and down, and abdominal wall musculature contracting and forcing abdominal contents upward into the thoracic cavity and increasing intrathoracic pressure.
Compared to adults, children, particularly infants, are at higher risk of acute respiratory failure. The small diameter of children's airway results in a high resistance to flow. Resistance is proportional to the inverse of the radius of the airway to the 4th power; thus, even small changes in the airway radius can result in large increases in airway resistance, leading to severely decreased airflow. The pediatric airway is small and can be further narrowed by secretions, edema, or bronchoconstriction. Young children also have underdeveloped collateral ventilation and an acute angle of the right upper lobe bronchus, predisposing them to atelectasis.4 The chest wall of a child is more compliant, which from a mechanical standpoint, is disadvantageous for normal breathing. The diaphragm of children fatigues quicker than adults due to fewer type-1 muscle fibers. Lastly, in young infants, the central control of breathing is immature and prone to apnea and bradypnea.5
Impairments in oxygenation or ventilation leading to respiratory failure are most often due to ventilation/perfusion (V/Q) mismatch. Although the ideal 1:1 ratio of ventilation to perfusion is rare, in acute lung disease the mismatch becomes more severe. Lung segments perfused but not ventilated are considered dead space (V/Q approaches infinity). Examples of dead space ventilation include anatomical dead space (large airways), pulmonary embolism, and severe pulmonary hypertension. Clearance of CO2 is impaired when dead space is increased, resulting in hypercarbia. Areas of the lung that have perfusion but no ventilation result in shunt physiology (V/Q = 0). In shunt physiology, blood passes from pulmonary artery to pulmonary vein without being exposed to an aerated alveolar membrane, resulting in hypoxemia. Examples of shunt are lung collapse and pulmonary arterial-venous connections. In most lung diseases, there is heterogeneity in V/Q mismatch from 0 to infinity (Figure 1).
Three alveolar capillary units depicting normal (V/Q = 1), dead space (V/Q approaching infinity), and shunt (V/Q = 0) physiologies. V/Q, ventilation/perfusion.
Respiratory failure may also be the result of impaired diffusion of oxygen across the alveolar-capillary membrane. Diffusion limitation may coexist with V/Q mismatch. An example of diffusion impairment is pulmonary fibrosis. Hypercarbia due to diffusion impairment is rare because CO2 diffuses across the alveolar-capillary membrane more rapidly than oxygen.
Acute respiratory failure has three major etiological categories: intrinsic and acquired lung disease, airway disorders, and neuromuscular dysfunction (Table 1). Diseases that lead to respiratory failure from pulmonary pathology are caused by V/Q mismatching, gas diffusion impairment, or both. Airway disorders more commonly lead to respiratory failure in more children than adults due to the smaller radius of the airway. Neuromuscular causes of respiratory failure can occur anywhere from the central nervous system to the innervated muscles of respiration.
Causes of Acute Respiratory Failure
The initial assessment of children with concern for impending acute respiratory failure aims to determine the degree of respiratory impairment. Experienced clinicians can make this determination quickly at the bedside by astute observation. Assessment of patient vital signs, general appearance, lung examination, and mental health status allow for a rapid determination of the severity of illness and often suggest which interventions may be required to appropriately intervene to reverse the course of illness or to avoid respiratory arrest. Tachypnea and hypoxemia are common manifestations of acute respiratory failure, although tachycardia is often an underappreciated sign of impending respiratory failure. Increased work of breathing manifests as retractions, grunting, head bobbing, nasal flaring, or belly breathing. Children with respiratory failure due to neuromuscular weakness or central nervous system dysfunction may not exhibit typical signs of increased respiratory effort, thus a higher index of suspicion is warranted; an arterial blood gas should be obtained to aid the specific diagnosis.
Auscultation of the lung fields is helpful for both diagnosis and management. Prolonged exhalation or audible wheeze is suggestive of lower airway bronchoconstriction. Localized findings suggest a focal pneumonia or foreign body aspiration. Absence of breath sounds can be due to pneumothorax, pleural effusion, or dense consolidation of lung. Rales in all lung fields is commonly due to pulmonary edema or diffuse interstitial edema. Stridor is generated by turbulent airflow secondary to narrowing in the upper airway and may occur in croup, external airway compression, and high foreign body aspiration.
Altered mental status may be a cause or consequence of respiratory failure. Patients who are hypercarbic present with somnolence, whereas hypoxic patients are often agitated due to the lack of oxygen delivery to the end organs including the central nervous system. Children with traumatic brain injury and a Glascow Coma Score of 8 or less should be promptly intubated for airway protection. The use of the Glascow Coma Score for nontraumatic causes of altered mental health status is less well established but provides a common language for communicating an objective measure to trend over time. A neurological examination, particularly mental health status and strength, is important to help identify neuromuscular causes of respiratory failure.
The initial evaluation of a child in respiratory distress includes a targeted but thorough history and physical examination. A thorough history directed at identifying inciting signs and symptoms may aid clinicians in the underlying etiology of the acute respiratory failure. Initial laboratory data include blood gas sampling to assess acid/base status as well as oxygenation and ventilation. Arterial blood gas is preferred to venous blood gas due to the ability to assess oxygenation.
Chest radiography will frequently identify the inciting cause of respiratory failure including inflammatory or infectious conditions, radiopaque foreign bodies, atelectasis, or effusions. Chest radiograph also assesses for pathology that needs emergent intervention such as pneumothorax. Neither the chest radiograph nor the results of the blood gas analysis should delay the emergent management of an acutely deteriorating patient who requires intubation and mechanical ventilation.
Respiratory secretions can be sent for microbiologic, cytology, and histologic testing. A variety of methods can be used to sample secretions. The gold standard bronchoscopy with bronchoalveolar lavage (BAL) is the most invasive method but has the advantages of obtaining the deepest lung sample and visualizing the airways. If an infectious source of respiratory failure is suspected, the secretions are sent for the following laboratory tests: gram stain, acid fast bacillus stain, cell count, bacterial culture (possibly also fungal and mycobacterial culture), and/or viral polymerase chain reaction. BAL can also diagnose pulmonary hemorrhage, pulmonary hemosiderosis, and aspiration pneumonitis.
Supportive respiratory care is the mainstay of management. Classically, this consists of endotracheal intubation and mechanical ventilation. Although invasive mechanical ventilation is still commonly employed, there has been a dramatic increase in the use of noninvasive respiratory support options.6 Noninvasive ventilation modalities include high flow nasal cannula oxygen (HFNCO2), continuous positive airway pressure (CPAP), and bi-level positive airway pressure (BiPAP).
HFNCO2 is a popular mode of respiratory support for infants and small children. At high flow rates the air delivered by nasal cannula is heated and humidified to avoid complications and for patient comfort. The physiological definition of “high flow” is a flow rate greater than minute ventilation. Minute ventilation is equal to respiratory rate times tidal volume. HFNCO2 improves acute respiratory failure by providing high FiO2 to treat hypoxia and by providing positive pressure in the alveoli and small airways to help reduce work of breathing.7 In larger patients, HFNCO2 may be used to improve oxygenation but flow rates must be high (30–60 L/min) to improve the work of breathing.8 Although continuous positive pressure is supplied, HFNCO2 should not be used as a substitute for CPAP where an actual end-expiratory pressure can be targeted.
Mask CPAP and BiPAP are classic modalities for noninvasive ventilation. CPAP provides a single pressure throughout the respiratory cycle to maintain lung expansion. Patients can breathe spontaneously around the CPAP pressure. BiPAP is a synchronized mode of ventilation that provides an inspiratory pressure to assist with ventilation in addition to the lower continuous positive end-expiratory pressure. CPAP and BiPAP are usually delivered through a tight-fitting mask that covers the nose or nose and mouth. The masks needed for CPAP and BiPAP can lead to facial skin breakdown and aspiration of secretions or emesis.
Certain patient populations clearly benefit from noninvasive ventilation to try to stave off intubation and mechanical ventilation.9 Patients with asthma are notoriously difficult to ventilate after intubation due to air trapping from persistent bronchospasm. Conversely, they often respond well to BiPAP with decreased work of breathing.9–11 BiPAP is also helpful in patients with neuromuscular weakness, as it aids both inspiration and maintenance of lung recruitment. The use of noninvasive ventilation modalities has shown promise in reducing the incidence of intubation.11 However, lack of improvement of oxygenation and ventilation early after noninvasive ventilation measures are started is associated with need for intubation, thus patients must be assessed frequently to evaluate their response to these interventions.12
Invasive positive pressure ventilation with endotracheal intubation is often required in pediatric acute respiratory failure. Indications for intubation are failure of oxygenation or ventilation despite noninvasive respiratory support or patients' inability to protect their own airway. Intubation should be performed by or in the presence of a clinician with expertise in pediatric airway management. Intubation is generally safe but there is a 6% risk of severe complication, including a 1.7% chance of cardiac arrest.12 Possible difficult airways should be identified early, including craniofacial abnormalities, difficulty opening mouth, contraindication to extending neck or prior history of difficult intubation. The basic set of equipment needed for endotracheal intubation is shown in Table 2. Recently, there has been an increase in the use of video laryngoscopy.13
Intubation Equipment Checklist
Most children with acute respiratory failure are managed with conventional mechanical ventilation after intubation. Strategies for mechanical ventilation drastically changed after data revealed a 25% relative reduction in mortality in adults with ARDS when ventilated with a low-tidal volume strategy (6 mL/kg vs 12 mL/kg).14 Some pediatric studies have replicated similar benefits.15,16 Patients with hypoxia requiring greater than 0.4 FiO2 are treated with higher peak end expiratory pressure to maintain appropriate oxygenation while limiting toxic O2 exposure to the lungs.17
Children who fail conventional mechanical ventilation due to hypoxia can be transitioned to high-frequency oscillatory ventilation (HFOV). This ventilator uses a high mean airway pressure to maintain lung recruitment while using very small tidal volumes. HFOV is theorized to prevent ventilator-induced lung injury by avoiding high dynamic pressures in noncompliant lungs. In a study conducted before the era of low tidal volume ventilation, HFOV was shown to improve clinical outcomes in children.18 Two large adult trials have shown no mortality benefit of HFOV and possibly more adverse events.19,20
Inhaled nitric oxide selectively dilates the pulmonary arterioles and is a well-established treatment for pulmonary hypertension. It also has been used in patients with ARDS to improve V/Q matching in the absence of pulmonary hypertension. Inhaled nitric oxide will distribute to the well-ventilated areas of the lung and preferentially dilate the arterioles in those areas. Local blood flow increases, resulting in better V/Q matching. Inhaled nitric oxide has shown to improve oxygenation and extracorporeal membrane oxygenation (ECMO)-free survival but not mortality in adult patients with ARDS.21 Prone positioning has been used based on physiological arguments to improve V/Q matching. The adult data are mixed and the one large pediatric study did not show any clinical benefit.22,23
In patients who cannot be oxygenated or ventilated by conventional or advanced mechanical ventilation techniques, ECMO may be required. For refractory hypoxia or hypercarbia, the preferred modality is veno-venous extracorporeal membrane oxygenation (VV-ECMO). Venous blood is removed from the body with subsequent clearance of CO2 and oxygenation via an external artificial membrane, and returned to the right side of the heart. Currently, 64% of children placed on VV-ECMO will survive.24
Weaning from mechanical ventilation requires improvement in underlying pathophysiology. Patients must be on acceptably low ventilator settings before extubation. The patient must also be neurologically able to spontaneously breathe and protect their airway. Secretions must not be excessive, especially in smaller children. Children may need to transition to noninvasive support after extubation until their respiratory insufficiency has resolved.
Acute respiratory failure in children is a common cause of admission to the PICU with favorable outcomes for most patients. Prognosis is mainly dependent on the underlying etiology of the respiratory impairment. A minority of patients will be unable to wean from the ventilator and progress to chronic respiratory failure requiring tracheostomy and long-term mechanical ventilation.
- Wong JJ, Jit M, Sultana R, et al. Mortality in pediatric acute respiratory distress syndrome: a systematic review and meta-analysis [published online ahead of print January 1, 2017]. J Intensive Care Med. doi:10.1177/0885066617705109 [CrossRef].
- Schouten LR, Veltkamp F, Bos AP, et al. Incidence and mortality of acute respiratory distress syndrome in children: a systematic review and meta-analysis. Crit Care Med. 2016;44(4):819–829. doi:10.1097/CCM.0000000000001388 [CrossRef].
- North JB, Jennett S. Abrnormal breathing patterns associated with acute brain damage. Arch Neurol. 1974;31(5):338–344. doi:10.1001/archneur.1974.00490410086010 [CrossRef]
- Terry PB, Traystman RJ. The clinical significance of collateral ventilation. Ann Am Thorac Soc. 2016;13(12):2251–2267. doi:. doi:10.1513/AnnalsATS.201606-448FR [CrossRef]
- Schroeder AR, Mansbach JM, Stevenson M, et al. Apnea in children hospitalized with bronchiolitis. Pediatrics. 2013;132(5):e1194–e1201. doi:. doi:10.1542/peds.2013-1501 [CrossRef]
- Mayordomo-Colunga J, Pons-Odena M, Medina A, et al. Non-invasive ventilation practices in children across Europe [published online ahead of print March 24, 2018]. Pediatr Pulmonol. doi:10.1002/ppul.23988 [CrossRef].
- Pham TM, O'Malley L, Mayfield S, Martin S, Schibler A. The effect of high flow nasal cannula therapy on the work of breathing in infants with bronchiolitis. Pediatr Pulmonol. 2015;50(7):713–720. doi:. doi:10.1002/ppul.23060 [CrossRef]
- Mauri T, Grasselli G, Jaber S. Respiratory support after extubation: noninvasive ventilation or high-flow nasal cannula, as appropriate. Ann Intensive Care. 2017;7(1):52. doi:. doi:10.1186/s13613-017-0271-8 [CrossRef]
- Beers SL, Abramo TJ, Bracken A, Wiebe RA. Bilevel positive airway pressure in the treatment of status asthmaticus in pediatrics. Am J Emerg Med. 2007;25(1):6–9. doi:. doi:10.1016/j.ajem.2006.07.001 [CrossRef]
- Rabinstein AA. Noninvasive ventilation for neuromusucular respiratory failure: when to use and when to avoid. Curr Opin Crit Care. 2016;22(2):94–99. doi:10.1097/MCC.0000000000000284 [CrossRef].
- Yanez LJ, Yunge M, Emilfork M, et al. A prospective, randomized, controlled trial of noninvasive ventilation in pediatric acute respiratory failure. Pediatr Crit Care Med. 2008;9(5):484–489. doi:. doi:10.1097/PCC.0b013e318184989f [CrossRef]
- Nishisaki A, Turner DA, Brown CA 3rd, et al. A National Emergency Airway Registry for children: landscape of tracheal intubation in 15 PICUs. Crit Care Med. 2013;41(3):874–885. doi:. doi:10.1097/CCM.0b013e3182746736 [CrossRef]
- Grunwell JR, Kamat PP, Miksa M, et al. Trend and outcomes of video laryngoscope use across PICUs. Pediatr Crit Care Med. 2017;18(8):741–749. doi:. doi:10.1097/PCC.0000000000001175 [CrossRef]
- Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler AThe Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–1308. doi:. doi:10.1056/NEJM200005043421801 [CrossRef]
- Erickson S, Schibler A, Numa A, et al. Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study. Pediatr Crit Care Med. 2007;8(4):317–323. doi:10.1097/01.PCC.0000269408.64179.FF [CrossRef].
- Khemani RG, Conti D, Alonzo TA, Bart RD 3rd, Newth CJ. Effect of tidal volume in children with acute hypoxemic respiratory failure. Intensive Care Med. 2009;35(8):1428–1437. doi:. doi:10.1007/s00134-009-1527-z [CrossRef]
- Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327–336. doi:. doi:10.1056/NEJMoa032193 [CrossRef]
- Arnold JH, Hanson JH, Toro-Figuero LO, Gutierrez J, Berens RJ, Anglin DL. Prospective, randomized comparison of high-frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure. Crit Care Med. 1994;22(10):1530–1539. doi:10.1097/00003246-199422100-00006 [CrossRef]
- Ferguson ND, Slutsky AS, Meade MO. High-frequency oscillation for ARDS. N Engl J Med. 2013;368(23):2233–2234. doi:10.1056/NEJMc1304344 [CrossRef].
- Young D, Lamb SE, Shah S, et al. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med. 2013;368(9):806–813. doi:. doi:10.1056/NEJMoa1215716 [CrossRef]
- Bronicki RA, Fortenberry J, Schreiber M, Checchia PA, Anas NG. Multicenter randomized controlled trial of inhaled nitric oxide for pediatric acute respiratory distress syndrome. J Pediatr. 2015;166(2):365–9.e1. doi:. doi:10.1016/j.jpeds.2014.10.011 [CrossRef]
- 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;294(2):229–237. doi:. doi:10.1001/jama.294.2.229 [CrossRef]
- Scholten EL, Beitler JR, Prisk GK, Malhotra A. Treatment of ARDS with prone positioning. Chest. 2017;151(1):215–224. doi:. doi:10.1016/j.chest.2016.06.032 [CrossRef]
- ECMO Registry of the Extracorporeal Life Support Organization. ECLS registry report. International summary, January 2017. https://www.elso.org/Portals/0/Files/Reports/2017/International%20Summary%20January%202017.pdf. Accessed June 25, 2018.
Causes of Acute Respiratory Failure
Acute respiratory distress syndrome due to sepsis or trauma
Neuropathy (ie, Guillain-Barré syndrome)
Neuromuscular junction disorders (ie, myasthenia gravis)
Central nervous system dysfunction (travel, infection, seizure)
Intubation Equipment Checklist
Sedation and analgesia
Bag attached to O2 source
Appropriately sized mask
Suction catheter attached to suction
Size = (age + 4)/4
Cuffed tube one-half size smaller
Device or tape to secure tube
Color change thing