Acute Respiratory Failure

James Schneider,

MD*,

Todd Sweberg,

MD

INTRODUCTION

Acute respiratory failure is a common dilemma faced by pediatric critical care practitioners.
As many as two-thirds of pediatric intensive care unit (PICU) patients will be
admitted with a diagnosis of respiratory failure,1 which represents a common end
point to multiple pathologic processes, categorized as hypoxemic, hypercapnic,
or mixed. Common causes are listed in Table 1. In 2012, primary infections of the
lung were responsible for 2% of all mortalities in children younger than 5 years in
the United States and 18% worldwide.2 Developmental variations contribute to
the diverse etiologies and higher incidence of acute respiratory failure in children
compared with adults. Infants have more compliant chest walls than adults, making
it more difficult to generate the negative intrathoracic pressure required to inspire sufficient
tidal volumes in conditions of decreased lung compliance (ie, pneumonia, hyaline
membrane disease). The infant chest wall also has less elastic recoil. Further, collateral
ventilation through pores of Kohn or Lambert are not well developed in early
life. These characteristics make young children more susceptible to alveolar collapse.
Childhood airways lack the more rigid cartilaginous supports that strengthen into
The authors do not have any financial conflict of interest to disclose.
Division of Critical Care Medicine, Hofstra North Shore-LIJ School of Medicine, Cohen Childrens
Medical Center of New York, North Shore Long Island Jewish Health System, 269-01 76th
Avenue, New Hyde Park, NY 11040, USA
* Corresponding author.
E-mail address: [email protected]

KEYWORDS
_ Acute respiratory failure _ Pediatrics _ Acute lung injury _ Monitoring
_ Respiratory physiology
KEY POINTS

_ Acute respiratory failure is common in critically ill children.

_ Monitoring for respiratory failure includes commonly used invasive tests, such as blood
gas analysis, but noninvasive monitoring has recently grown in importance and proven
reliable.
_ Recent advancements in therapeutic options for respiratory failure have improved the
overall outcome of critically ill children, but much more rigorous investigation is still
needed.
Crit Care Clin 29 (2013) 167183
http://dx.doi.org/10.1016/j.ccc.2012.12.004 criticalcare.theclinics.com
0749-0704/13/$ see front matter _ 2013 Elsevier Inc. All rights reserved.

adulthood, making them more susceptible to dynamic compression and subsequent

airway obstruction in disease states associated with increased airway resistance
(ie, bronchiolitis, asthma). Last, the pediatric airways are naturally smaller in diameter
than in adults. Because the resistance to airflow is inversely proportional to the fourth
power of the radius (R 5 8NL/pr4), any narrowing of the pediatric airway will have
a much greater impact on the resistance. This will lead to a more profound decrease
in airflow, as laminar flow transitions to turbulent flow, as described by Reynolds
number (Re 5 2 rVr/N, where r is the radius of the airway, V is the velocity of the
gas flow, r is the density of the gas, and N is the viscosity of the gas). In the adult,
the peripheral airways contribute about 20% of the total airway resistance. In infants
and young children, they contribute about 50%, explaining why diseases affecting the
peripheral airways (ie, bronchiolitis) have such a profound clinical impact. It is clear
that the management of acute respiratory failure in children requires a thorough understanding
of these physiologic differences, reminding the clinician that children are, in
fact, not little adults.
Acute respiratory failure occurs when embarrassment of the respiratory system
results in the inability to properly transfer oxygen (O2) from the atmosphere to the
blood or remove carbon dioxide (CO2) from the blood and eliminate it to the atmosphere.
Hypoxic respiratory failure is defined by a partial pressure of arterial
O2 (PaO2) that is less than 60 mm Hg on room air at sea level, and hypercapnic respiratory
failure occurs when the partial pressure of CO2 (PaCO2) is greater than 50 mm
Hg (with a concomitant respiratory acidosis) under the same conditions. To better

understand these, it is first important to examine the mechanisms of oxygenation

and ventilation.
Table 1
Etiologies of acute respiratory failure in children
Location Example
Upper airway obstruction _ Infection (croup, epiglottitis, bacterial tracheitis)
_ Laryngotracheomalacia
_ Foreign body
_ Anaphylaxis
Lower airway obstruction _ Asthma
_ Bronchiolitis
_ Cystic fibrosis
Restrictive lung disease _ Acute respiratory distress syndrome
_ Pleural effusion
_ Pneumonia
_ Pulmonary edema
_ Abdominal compartment syndrome
Central nervous system disorder _ Intracranial injury (hemorrhage, ischemia)
_ Medication (sedatives)
_ Metabolic encephalopathy
Peripheral nervous system and
muscle disorders
_ Guillian Barre syndrome
_ Muscular dystrophy
_ Scoliosis
_ Spinal cord injury
_ Botulism
_ Intoxications (ie, organophosphates)
Adapted from Ghuman AK, Newth CJ, Khemani RG. Respiratory support in children. Paediatr Child
Health 2011;21(4):1639; with permission.

168 Schneider & Sweberg

Oxygenation

Ideally, oxygen that is contained within the alveolus at inspiration will equilibrate with
arterial blood, as described by the alveolar gas equation:
PAO2 5 PIO2 (PACO2/R),
then PAO2 5 FiO2 (PB PH2O) PACO2/R,
where PAO2 5 partial pressure of alveolar oxygen; PIO2 5 partial pressure of inspired
oxygen; PACO2 5 partial pressure of alveolar CO2 (substituted by arterial [PaCO2] due
to the highly efficient manner that CO2 crosses cell membranes); R 5 respiratory
quotient: ratio ofCO2 production (VCO2) toO2 consumption (VO2) (R5VCO2/VO2), averages
0.8 on a normal, mixed adult diet; PB 5 barometric pressure; and PH2O 5 water
vapor pressure.
Adequate gas exchange also requires that the inspired alveolar gas matches blood
distribution in the pulmonary capillaries. There is a normal gradient between alveolar
and arterial PO2, known as the A-a gradient, which is less than 10 mm Hg. The alveolar
gas equation also helps to understand some of the mechanisms behind hypoxemia
(Box 1).3 Nonpulmonary causes, such as decreased cardiac output, increased extraction
of O2, and abnormal hemoglobin, can also contribute to abnormal gas exchange. 4
The most common etiology for hypoxemia in critically ill children is inequality in the
relationship between ventilation and perfusion (V/Q). Regional differences in ventilation
and blood flow, owing to regional differences in intrapleural pressures and gravitational
forces, cause ventilation and perfusion to decrease from the base to the apex
of the lung, although perfusion does so much more rapidly. This leads to an abnormally
high V/Q ratio at the apex of the lung (in an upright position) and a much lower
one at the base.3 Atelectasis from various pathologic states (ie, pneumonia, mucous
plug) exaggerates the mismatching of V/Q, causing well-oxygenated blood from high
V/Q regions to mix with poorly oxygenated blood from low V/Q regions, leading to
worsening hypoxia with an increased A-a gradient. Pulmonary edema (ie, cardiac
failure, systemic inflammatory response syndrome, acute respiratory distress
syndrome [ARDS]) will lead to worsening V/Q mismatching, compromised diffusion,
and atelectasis. Hypoxemia caused by V/Q inequality can be corrected by inspiring

a higher concentration of oxygen, as well as the provision of positive pressure ventilation,

which may recruit consolidated or collapsed lung units and improve V/Q
matching.
When alveolar ventilation is decreased, insufficiently replenishing alveolar oxygen,
the alveolar PO2 falls as the PCO2 rises, not altering the normal A-a gradient. Elevation
of PaCO2 that occurs with airway obstruction will not result in hypoxemia until severe
obstruction is present, with forced expiratory volume in 1 second less than
Box 1
Causes of hypoxemia
Hypoventilation
Shunt
Ventilation-perfusion inequality
Diffusion limitation
Low inspired fraction of oxygen

Acute Respiratory Failure 169

approximately 15% predicted.5 The hypoxia that results from CO2 retention is easily
overcome with the addition of increased inspired oxygen.
Shunting describes the direct mixing of deoxygenated venous blood that has not
undergone gas exchange in the lungs with arterial blood. Normal anatomic shunting
occurs as venous blood from the bronchial veins and Thebesian veins collects in
the left-sided circulation. Pathologically, patients may have abnormal vascular
connections (ie, arterial-venous fistula) or intracardiac communications allowing blood
to traverse the heart from the right to the left without undergoing gas exchange at the
level of the lungs. Intrapulmonary shunting most commonly occurs as blood perfuses
regions of the lung that are not well ventilated. The addition of mixed venous blood
(with depressed PO2) to oxygenated capillary blood results in decreased PaO 2,
increasing the A-a gradient. The amount of shunted blood that would need to be mixed
with arterial blood to account for the A-a gradient can be calculated by the shunt
equation:
QS/QT 5 (CcO2 CaO2)/(CcO2 CvO2),
where QS is shunt flow to unventilated lung units; QT is total pulmonary blood flow; and
CaO2, CcO2, and CvO2 is the content of oxygen in arterial, end-capillary, and mixed
venous blood, respectively.3 In healthy individuals, normal physiologic shunting
accounts for less than 5% of cardiac output.6 The addition of supplemental oxygen,
increasing the PAO2, has minimal effect on improving the hypoxemia, as the shunted
blood is not exposed to the high alveolar PO2.
Diffusion of oxygen between the alveolus and capillary blood can be altered by
thickening of the alveolar-capillary barrier, by decreased alveolar capillary volume,
or increased oxygen extraction. Further, decreasing the PAO2 at high altitude
decreases the alveolar-capillary PO2 pressure gradient, limiting diffusion. Diffusion
impairment is a rare primary cause of hypoxemia in children, although it can contribute
to the hypoxemia associated with shunt and V/Q mismatching. More than 50% of the
diffusion capacity of the lung must be compromised to develop hypoxemia from
primary diffusion limitation. Supplemental oxygen can rapidly overcome hypoxemia
associated with diffusion limitations.
Ventilation

Exchange of CO2 follows similar physiologic principles to O2. Because of differences

in the solubility, dissociation curves of CO2 and O2, as well as the way each gas effects
central ventilatory control, CO2 exchange (and invariably PaCO2) is ultimately determined
by alveolar minute ventilation and the degree of dead space present. PaCO 2
is related to the balance between the production of CO2 (VCO2), which is a function
of the metabolic conditions of the patient, and the alveolar minute ventilation (V A),
as described by the equation:
PACO2 5 VCO2 * K/VA
Minute ventilation is determined by the product of the respiratory frequency (f) and
the tidal volume (Vt). Dead space gas, both anatomic (in the conducting airways) and
physiologic (areas of ventilation lung units that are poorly perfused; V>Q), does not
participate in CO2 elimination. Therefore, total alveolar ventilation is determined by
the difference between total minute ventilation (VE) and the degree of dead space
ventilation (VD):

VA 5 VE VD
170 Schneider & Sweberg

As a result, elevations in PaCO2 will result from conditions of decreased tidal volume
or increased physiologic dead space (Table 2). Ventilatory muscles generally can
maintain adequate tidal volumes with only 50% of normal strength. 7 Hyperinflation
further compromises respiratory muscle function. Diseases associated with airway
obstruction increase the end expiratory lung volume greater than functional residual
capacity (FRC), decreasing muscle fiber length below what is optimal. Muscle fibers
generate less force at these shorter lengths.8 Similarly, hyperinflation causes a flattening
of the diaphragm, putting it at a mechanical disadvantage.
V/Q mismatching generally does not cause a direct increase in PCO2 because
elevated CO2 from low V/Q units is a potent stimulator of the central respiratory
centers, increasing alveolar minute ventilation.3
EPIDEMIOLOGY

As a common end point to multiple clinical conditions, the incidence of respiratory

failure in the pediatric population is difficult to ascertain. In one study, 17.1% of
patients admitted to a PICU at several large childrens hospitals required mechanical
ventilation, with acute respiratory conditions as the culprit in 62.4% of these patients.
In this cohort of patients, bronchiolitis (26.7%) and pneumonia (15.8%) were the
leading etiologies for respiratory failure.9
Acute lung injury (ALI) accounts for 12.8 cases per 100,000 person years, with an
in-hospital mortality rate of 18% to 22%10,11; 10% of intubated children admitted to
a European PICU had ALI, with a mortality rate of 27%. Of the patients with ALI,
54% had ARDS at presentation and 80% progressed to ARDS at some point during
their hospitalization.12
Bronchiolitis, both respiratory syncytial virus (RSV) and non-RSV, accounts for up to
16% of all hospital admissions, with RSV bearing responsibility for 1 of every 334
hospitalizations.13,14 From 7.4% to 28.0% of children with bronchiolitis require
mechanical ventilation. The burden of RSV is more severe at younger age and in
patients with chronic disease. Of all RSV admissions, for both bronchiolitis and pneumonia,
4% require intubation and mechanical ventilation. 15
Table 2
Causes of hypercarbia
Decreased Tidal Volume Increased Dead Space
Sedative overdose:
_ Opioid
_ Benzodiazepine
Hyperinflation
_ Obstructive airway disease
_ Asthma
_ Bronchiolitis
_ Cystic fibrosis
_ Excessive PEEP on mechanical ventilator
Neuromuscular weakness
_ Central nervous system disease
_ Spinal cord injury/inflammation
_ Peripheral nerve disorder
_ Neuromuscular junction disease
_ Myopathy
_ Metabolic derangements
Decreased cardiac output
_ Dehydration
_ Dysrhythmia
_ Myocarditis/cardiomyopathy
_ Post cardiopulmonary bypass
Flail chest (post trauma) Increased pulmonary vascular resistance
Pulmonary embolism

Acute Respiratory Failure 171

Respiratory failure in asthmatic individuals has declined over time, as novel therapies
have emerged. Current intubation rates vary widely for asthmatic patients, from
5% to 17% based on presentation to a community hospital or tertiary care center,
with a higher rate for those presenting to community hospitals. 16
MONITORING

Monitoring respiratory function appropriately will help identify the development of

respiratory failure as well as guide therapy based on response, and can predict
outcome.17 The fundamental and most important assessment of respiratory function
is the clinical examination. Respiratory rate and pattern are indicative of the physiologic
status of the respiratory system. Tachypnea is often the first sign of respiratory
compromise.18,19 Dys-coordinate, paradoxic movement of the chest during breathing
is evidence of impending respiratory failure and requires immediate attention. 20
Infants and young children may present with grunting in an attempt to increase their
positive end-expiratory pressure and maintain functional residual capacity, indicating
the presence of restrictive lung disease.21 Cyanosis is evident when greater than 3 to
5 g/dL of deoxygenated hemoglobin is present in arterial blood. This correlates with an
arterial saturation of 80% in healthy individuals, but is unreliable in conditions of
anemia, or in the presence of abnormal forms of hemoglobin, such as methemoglobin
or carboxyhemoglobin.
Traditionally, adequacy of gas exchange has been monitored by invasive means,
in particular blood gas analysis. The arterial blood gas (ABG) is the gold standard
for PO2 determination, as it reliably measures PO2 directly. The percent oxyhemoglobin
saturation from a blood gas is highly unreliable, as it is a calculated value
based on temperature, PaCO2, pH, and PaO2. Free-flowing capillary blood can
accurately assess pH and PaCO2.2225 Peripheral venous samples are unreliable
for estimating pH or PaCO2,22,26,27 and should be avoided for clinical decisions
regarding ventilation.
Since the 1980s, noninvasive monitoring of oxygenation has been available in the
form of pulse oximetry (SpO2). Pulse oximeters are accurate when oxyhemoglobin
concentrations are greater than 60%, but may not be reliable in conditions of poor
perfusion (ie, septic shock), peripheral vasoconstriction (ie, norepinephrine), hypothermia,
peripheral edema, significant extremity movement, or in the presence of
methemoglobin or carboxyhemoglobin. Other important clinical data can be interpreted
by the pulse oximeter as well, such as heart rate, rhythm, and peripheral perfusion.
28,29 The presence of pulsus paradoxus, indicated by respiratory variability in the
pulse oximeter plethysmography tracing, correlates with important upper airway
obstruction (eg, croup), as well as degree of lower airway obstruction (eg, asthma),
and offers a continuous and accurate evaluation of response to therapy (Fig. 1).30,31
Pediatric intensivists frequently substitute pulse oximetry for arterial catheters while
caring for critically ill children with respiratory failure, with management decisions
and outcomes remaining equal.32
Similarly, ventilation can be monitored continuously and noninvasively. Capnography
monitors detect CO2 levels, determined by its unique infrared light absorption
characteristics. Capnography can be used at the end of the endotracheal tube in
intubated patients or in nonintubated patients by nasal cannula during procedural
sedation to assess the quality of ventilation.3335 Table 3 lists the many clinical uses
of capnography waveforms (Fig. 2). Generally, end-tidal CO2 (ETCO2) is about 1 to
3 mm Hg lower than PaCO2 in healthy individuals owing to physiologic dead space
ventilation. In fact, the difference between the ETCO2 and PaCO 2 directly correlates
172 Schneider & Sweberg

with the degree of dead space present, and can be used to estimate dead space ventilation
according to the Bohr equation:
VD/VT 5 (PACO2 PECO2)/PACO2
Therefore, continuous capnography can be used to detect alterations in dead space
ventilation and response to therapeutic interventions.
Severe respiratory illness, such as ALI or ARDS, has traditionally been monitored
and defined based on the severity of hypoxemia according to invasive measurements
of PaO2.36 See Box 2 for diagnostic criteria for ALI/ARDS. The severity of hypoxemia
has been determined by the ratio of PaO2 to the fraction of inspired oxygen (PaO2/FiO2).
The oxygenation index (OI) is commonly used as a superior indication of oxygenation
impairment, as it takes into account the level of ventilatory support provided ([OI 5 FiO2
* mean airway pressure]/PaO2). Unlike in adults, the degree of hypoxemia in children
is associated with mortality,1,11,3740 length of mechanical ventilation,38,39 and the
Fig. 1. Pulse oximeter waveforms. Solid line: normal. Broken line: evidence of pulsus paradoxus.
Arrow indicates inspiration and concordant decrease in peak of plethysmography

tracing, indicating cardiovascular consequence of increased work of breathing, generating

a more negative intrapleural pressure. This can be seen in upper airway obstruction
(ie, infectious croup, postextubation) or lower airway obstruction (ie, asthma) and improves
with appropriate therapy.
Table 3
Clinical conditions determined by use of capnography
Increase in ETCO2 Decrease in ETCO2
Hypoventilation Unplanned extubation
Administration of sodium bicarbonate Endotracheal tube obstruction
Increase in cardiac output Ventilator disconnection
Increased dead space
Pulmonary embolism
Decreased cardiac output
Continuous capnography also allows for accurate evaluation of respiratory rate, rhythm, and
patient-ventilator asynchrony.
Abbreviation: ETCO2, end-tidal carbon dioxide.

Acute Respiratory Failure 173

development of chronic lung disease in neonates.41 A significant proportion of children

with acute hypoxemic respiratory failure are managed without arterial lines, and therefore
cannot be classified as ALI/ARDS.32 Noninvasive correlates of severity of hypoxemia
have now been established, as the definition of ALI/ARDS is being reconsidered.
The SpO2/FiO2 ratio (substituting SpO2 for PaO2), as well as the OSI (oxygen saturation
index, substituting SpO2 for PaO2) are gaining specific attention as validated measures
of hypoxemia.4244 Further, with the use of noninvasive measures, up to 35% more
patients could be captured for pediatric studies of ALI. 32
THERAPY

Specific aspects of the therapy for respiratory failure vary depending on the underlying
cause. In all cases, however, the goal of therapy is to supplement the patients
Fig. 2. Capnograph (time-based). Solid line: normal. Phase I: dead space (anatomic) gas
exhaled from conducing airways; CO2 content near zero. Phase II: mixing of alveolar gas,
which contains CO2. Phase III: plateau phase corresponds to pure alveolar gas. Phase IV:
rapid fall due to inspiration, with negligible CO2. x and x: ETCO2. Dotted line: obstructed
airway disease. Phase III slopes upward because of delay in emptying of alveolar gas from
different lung units owing to increased airway resistance. The upsloping directly correlates
with degree of obstruction, and improves with response to bronchodilator therapy. (Data
from Krauss B, Deykin A, Lam A, et al. Capnogram shape in obstructive lung disease. Anesth
Analg 2005;100(3):8848; and Yaron M, Padyk P, Hutsinpiller M, et al. Utility of the expiratory
capnogram in the assessment of bronchospasm. Ann Emerg Med 1996;28(4):4037.)
Box 2
Consensus criteria for definition of acute lung injury or acute respiratory distress syndrome
Acute onset
Bilateral infiltrates on chest radiograph
Severe hypoxemia resistant to oxygen therapy
_ PaO2/FiO2 ratio _200 torr (_26.6 kPa) for ARDS
_ PaO2/FiO2 ratio _300 torr (_40 kPa) for ALI
No evidence of left atrial hypertension
_ Pulmonary artery occlusion pressure <18
Data from Bernard GR, Artigas A, Brigham KL et al. The American-European Consensus
Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination.
Am J Respir Crit Care Med 1994;149(3):81824.

174 Schneider & Sweberg

gas exchange. Initial measures should include steps to ensure airway patency and
clearance. Supplemental oxygen may be administered via facemask or nasal
cannula.
The use of noninvasive positive pressure ventilation (NPPV), in the form of continuous
positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP),
has gained widespread acceptance as a therapy for respiratory failure from a variety
of etiologies.4550 NPPV may supplement respiratory mechanics by unloading the
respiratory musculature, stabilizing the chest wall, and improving minute ventilation.
The recruitment of atelectatic alveolar units and improved clearance of intra-alveolar
fluid augment end expiratory lung volume, approaching FRC, and decrease the A-a

gradient.47
A number of disadvantages are intrinsic to NPPV that limit its utility. The risk of aspiration
is significant; therefore, enteral feeding is generally avoided, and gastric decompression
may be considered prophylactically. Patients, particularly those with
developmental or cognitive impairments, may experience substantial anxiety with
the placement of the BiPAP mask, risking proper positioning and function. Although
small doses of anxiolytics may be administered, caution must be taken when
providing respiratory depressants to patients with a native airway and impaired
pulmonary function.47
ALI/ARDS

The mainstay of therapy in the most severe forms of acute hypoxemic respiratory
failure is intubation and mechanical ventilation. The goal of mechanical ventilation in
this group of patients is to provide adequate gas exchange while avoiding
ventilator-associated secondary lung injury (VILI). Ventilation with high volumes and
pressures, cyclic opening and closing of alveoli, and delivery of high Fi O2 result in
a proinflammatory cascade causing lung injury and pulmonary edema. 51 By using
a lung-protective strategy using low tidal volumes of 6 to 8 mL/kg and limiting
plateau pressure to 30 or less, secondary lung injury may be curtailed. This approach
necessitates decrease in minute ventilation, with a concomitant respiratory acidosis.
Usual targets include a pH of 7.25 or higher, with a P CO2 of 60 to 80 torr, and oxygen
saturation goals of 88% or greater. Adult data have demonstrated significant improvement
in mortality with this approach.51 Although no large-scale pediatric studies have
been performed to date, this approach has gained widespread acceptance, 4,52 with
similar benefit noted in retrospective studies.53
Another approach to lung protective ventilation, or open lung strategy, is highfrequency
oscillatory ventilation (HFOV). HFOV allows for increased mean airway pressure
with decreased peak airway pressure, facilitating recruitment of atelectatic lung
segments, while avoiding the cyclic shearing open and subsequent alveolar collapse,
decreasing the risk of VILI. Over the past 20 years, HFOV has been used extensively in
the pediatric population; however, definitive data demonstrating clear clinical benefit
versus low tidal volume conventional ventilation are lacking. 54
Prone positioning has been suggested as an adjunctive therapy to ventilator
management. The prone position improves recruitment and clearance of alveolar
debris in dependent lung segments. Studies have documented an improvement in
oxygenation in the prone position, but have failed to demonstrate improvements
in ventilator-free days or survival.5557 A recent meta-analysis found that prone positioning
may reduce the relative risk of mortality in patients with PaO 2/FiO2 ratios of
less than 100 mm Hg by 16%, although it was associated with increased risk of
pressure ulcers, endotracheal tube obstruction, and chest tube dislodgement. 58
As such, prone positioning may be considered in those patients with the most
Acute Respiratory Failure 175

severe ARDS, although careful consideration of the risks and benefits must be
taken.
Another adjunctive therapy used in ARDS is inhaled nitric oxide (iNO). A potent,
locally acting pulmonary vasodilator, the aim of therapy is to overcome regional
hypoxic vasoconstriction and improve V/Q matching and oxygenation. Studies have
demonstrated an initial, albeit transient, improvement in oxygenation; however, no
improvement in clinically relevant outcomes, such as ventilator-free days or survival, 59
has been identified.
Qualitative and quantitative surfactant deficiencies occur in ARDS because of intraalveolar
edema and inflammatory mediators, as well as impaired production, resulting
in impaired pulmonary compliance.60 Replacement of surfactant in neonates with
meconium aspiration syndrome is well documented to result in improved pulmonary
mechanics and survival, and serves as the rational basis for studies in pediatrics. 61
Pediatric studies have demonstrated an improvement in oxygenation, ventilator-free
days, and survival.60,62 Specifically, benefit was identified in patients with ARDS
secondary to direct lung injury,60 although power was lacking to make definitive
recommendations for its use. Ongoing clinical trials are further exploring the utility

of this therapy.
Corticosteroids have been used for ARDS in an attempt to attenuate the inflammatory
process responsible for the syndrome. Although some studies have documented
an improvement in survival, others have failed to show benefit, with the
indication that steroids started after 14 days of the disease process may worsen
survival.63,64 As such, the use of steroids for ARDS remains a controversial therapy
at this time.
As previously described, fluid overload has a significant detrimental role on the
physiology and outcome of adults and children with ALI, 1,40,6567 specifically when
greater than 10% to 15%.1,66 No rigorous clinical trial has attempted to replicate
the 2006 ARDSNet fluid management trial65 in children. Nonetheless, conservative
fluid management while ensuring adequate cardiac output is a common strategy in
patients with ALI.52
The use of paralytic agents in patients with ARDS has recently shown promise. The
judicious use of neuromuscular blockade has been used to improve patient-ventilator
synchrony, although concerns about prolonged muscle weakness have persisted. In
an adult study, the use of cisatricurium within 48 hours of ARDS onset was demonstrated
to improve adjusted 90-day mortality and time off the ventilator, without an
increased incidence of muscle weakness.68 No pediatric data currently exist to guide
the use of neuromuscular blocking agents in respiratory failure.
Asthma

The mechanics of respiratory failure due to asthma and other obstructive pulmonary
processes are different than those related to ARDS and pneumonia, and require
different management strategies. As previously described, obstructive lung disease
results in air trapping and an increase in end expiratory lung volume over FRC, resulting
in increased intrinsic pulmonary pressure at end expiration, termed auto-PEEP.
This places the respiratory system at a mechanical disadvantage, in the face of
increased work of breathing required to initiate inspiration (to overcome the autoPEEP) as well as to overcome the resistance to airflow.
The act of intubation and initiation of positive pressure ventilation in a patient with
high levels of auto-PEEP bears additional risks, such as barotrauma and resultant
air leak syndrome. Adding positive pressure can further impair venous return to the
heart, which can result in compromised cardiac output and cardiac arrest. Significant
176 Schneider & Sweberg

efforts are therefore made to prevent intubation of asthmatic patients. These include
anti-inflammatory therapy with steroids, and bronchodilation with inhaled or intravenous
b-agonists. Other acute asthma adjuncts include magnesium, anticholinergics,
and methylxanthines. In-depth discussion on these therapies is beyond the scope
of this article.
The use of BiPAP has been advocated as a safe and effective way to realize some of
the benefits of positive pressure ventilation on the sick asthmatic patient without some
of the risks inherent in endotracheal intubation.49,69,70 By providing assistance to
inspiratory flow, BiPAP can help unload the respiratory muscles and decrease work
of breathing. Perhaps more importantly, the PEEP maintained at end exhalation stents
the small airways open, reducing airway collapse due to elevated intrathoracic pressures
and dynamic compression, and relieves hyperinflation. Further, PEEP decreases
the amount of negative intrathoracic pressure required to initiate a breath, reducing
the work of breathing.71
Helium-oxygen (heliox) gas mixture may be considered for severe asthma. Helium is
less dense than air, reducing the Reynolds number, improves laminar flow to and from
obstructed airways, and may help in delivery of aerosolized particles to the distal
airways.71,72 Heliox is available in concentrations ranging from 80%: 20% to 60%:
40% helium: oxygen, with the highest benefit derived from the highest helium concentration.
Heliox has been used to drive albuterol nebulization, and can be blended into
BiPAP and ventilator circuits. Limited studies have failed to show consistent benefit
with the use of heliox, with the suggestion of benefit in the most severe patients. 7173
More rigorous study is indicated before heliox can be routinely recommended for asthmatic
individuals with respiratory failure.

Intubation and mechanical ventilation may be required in patients who fail noninvasive
therapy. The general approach most frequently advocated is a prolonged exhalatory
phase, targeted to allow complete exhalation and reversal of the dynamic
hyperinflation. Monitoring should ensure that a complete exhalation has taken place
before the next ventilator breath is delivered, preventing worsening dynamic hyperinflation,
compromising gas exchange and cardiac function further. This requires low
respiratory rates with limitation of minute ventilation and accepting a concomitant
respiratory acidosis. A pH above 7.20 and PaCO 2 below 90 are generally accepted
goals.74,75 Volume control modes of ventilation offer a fixed tidal volume in patients
with dynamic changes in airway resistance, whose delivered volumes in pressure
control modes may vary significantly from breath to breath.
The role of PEEP for mechanically ventilated asthmatic individuals is controversial.
The use of PEEP may help overcome increased respiratory effort needed to overcome
auto-PEEP in the spontaneously breathing patient. In addition, PEEP may assist in
stenting open distal airways during exhalation, preventing dynamic collapse during
exhalation; however, PEEP itself provides an obstruction to exhalatory flow, with the
potential to worsen intrinsic air trapping.7476
Another approach to the intubated asthmatic individual is the use of pressure
support ventilation. Pressure support assistance during inspiration helps overcome
the resistance to airflow and decreases work of breathing. The patient determines
the rate, inspiratory and expiratory times, and flow pattern. High levels of PEEP are
applied to match the intrinsic PEEP created by the air trapping, titrated to the clinical
assessment of the patients work of breathing. By remaining unparalyzed, the patient
contributes to the reversal of hyperinflation with active exhalation. Although only case
reports on this approach are published to date, the possibility of minimizing the use of
paralytics in patients already at risk of muscle weakness caused by corticosteroid use
is attractive and bears further investigation.77
Acute Respiratory Failure 177

Bronchiolitis

Bronchiolitis is the result of airway inflammation, with subsequent secretions and

cellular debris, resulting in obstructive pulmonary disease. As a viral process, there
is no specific therapy and treatment is supportive. Multiple pharmacologic interventions,
including b-2 agonists, racemic epinephrine, and corticosteroids, have been
studied without convincing evidence of their efficacy. 78 Nasal CPAP is frequently
used for respiratory support in the sick individual with bronchiolitis. High-flow nasal
cannula appears to be a potential alternative, although further study is warranted. 79
If unresponsive to noninvasive therapy, intubation and pulmonary support while allowing
for lung recovery is indicated.
It is important to differentiate RSV bronchiolitis from RSV pneumonia, which tends
have a more prolonged course with greater lung injury.80 Those with RSV pneumonia
frequently meet ALI and ARDS criteria, and therapy is directed in that manner.
Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) has been used for cases of refractory
respiratory and cardiorespiratory failure since its widespread deployment in the late
1970s and early 1980s. Overall survival is 57% in pediatric patients (30 days to 18 years
old), with wide variation based on diagnosis, ranging from 39% (pertussis) to 83%
(asthma).81 As ECMO circuits have become more compact and easier to manage,
and greater expertise has been developed, ECMO has been offered to more complex
patients. Patients can be considered eligible candidates even after prolonged
mechanical ventilation for longer than 14 days.82 Nevertheless, ECMO remains a highly
invasive, costly, labor-intensive therapy that can be used only in centers experienced
in its use.
PROGNOSIS AND OUTCOME

Overall, the mortality from ALI is relatively high (22%27%) compared with the general
PICU population, although lower than in adults (35%45%). 37,83 Fortunately, mortality
for ALI continues to improve in children, recently reported as low as 8%, 56 although
higher for recipients of stem cell transplantation. 84 Interestingly, children with ARDS
secondary to RSV have a significantly lower mortality rate of approximately 5%
compared with ARDS from other causes.80 The degree of hypoxemia, as described

by PaO2/FiO2 ratio, SaO2/FiO2 ratio, OI, or OSI, and alveolar dead space fraction
(PaCO2-PETCO2/PaCO2), is associated with increased risk of death. 11,42,43,83 The
presence of central nervous system (CNS) dysfunction and non-CNS organ dysfunction
are also associated with an increased risk of mortality. 37
Although the prevalence of asthma in the pediatric population has increased in
recent years, the outcome in even those with respiratory failure is generally good.
The rate of invasive mechanical ventilation ranges from 3% to 47%, with an overall
mortality rate of 7% to 8%.85,86 Most are intubated outside the PICU (56%), with those
intubated in the PICU requiring longer durations of mechanical ventilation.
Survivors of acute hypoxemia respiratory failure have risk for both restrictive and
obstructive lung disease,12,8791 similar to adult survivors. Although most children
will have physiologic evidence of obstructive or restrictive disease after discharge
from the hospital, pulmonary function continues to recover over the first year after
the acute illness.89 Little improvement is seen subsequently, and evidence of altered
pulmonary function persists.88 Subjectively, though, many will have complete functional
recovery,88,91 although bronchodilators may be needed during exercise or an
intercurrent viral illness.
178 Schneider & Sweberg

Outcome reports vary, likely related to the timing of the follow-up. It has been suggested
that patient evaluations should occur 6 to 12 months after the acute illness,
after which any significant recovery of pulmonary function is unlikely. 89,9294
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Acute Respiratory Failure 179