Pediatric Acute Respiratory Distress Syndrome

Author: Andrew K Feng, MD; Chief Editor: Timothy E Corden, MD

http://emedicine.medscape.com/article/803573-overview#a0104
Pathophysiology
Acute lung injury follows a direct pulmonary or systemic insult resulting in injury to the alveolar-capillary
unit. Several diseases can cause ARDS, more commonly following pneumonia, aspiration, and sepsis.
The pathophysiology of ARDS is complex and multifaceted. It may be considered as 3 distinct
components: (1) the nature of the stimulus that initiates or causes ARDS, (2) the host response to this
stimulus, and (3) the role that iatrogenic damage plays in the progression and outcome of this condition.
The course of ARDS can be divided into 3 histopathologic stages, as follows:
Exudative: Injury to lung endothelial cells and alveolar epithelial cells occurs during days 1-7 of the initial
injury. Air spaces are then filled with exudate and fluid, and the development of microvascular thrombi
leads to capillary occlusion.
Proliferative: This stage occurs between the first and third week after the initial insult. Type II
pneumocytes, fibroblasts, and myofibroblasts proliferate, resulting in widening of the alveolar septa and
conversion of intra-alveolar hemorrhagic exudate into cellular granulation tissue.
Fibrotic: After 3 weeks from the time of injury, the lungs exhibit remodeling and fibrosis.
During the exudative stage, the initiating stimulus leads to a cascade of effects, the most immediate of
which is an increase in alveolar and pulmonary capillary permeability. Protein-rich fluid engulfs the
alveolus, activated neutrophils and macrophages follow, and an inflammatory cascade is initiated. This
cascade involves the release of interleukins (ILs), tumor necrosis factor (TNF), and other inflammatory
mediators. Neutrophils release oxidants, leukotrienes, and various proteases.
The net effect at a cellular level is massive cell damage, alveolar denudation, and sloughing of cell debris
into the lumen of the alveolus. Furthermore, surfactant is markedly inactivated.
Meanwhile, in the pulmonary capillary bed, endothelial cells swell, platelets aggregate, and a
procoagulant cascade arises, leading to small-vessel thrombosis.
On the clinical level, work of breathing increases secondary to surfactant depletion, alveolar filling, cellular
debris within the alveoli, and increased airway resistance. Surfactant loss leads to alveolar collapse
because of increased surface tension, which is analogous to the situation observed in premature infants
with infant RDS (IRDS). As alveoli collapse, closing lung volume capacity rises above the patients
functional residual capacity (FRC), further increasing atelectasis and the work of breathing. This is
reflected as reduced compliance; that is, additional pressure is required to generate a unit volume.
In addition, the remaining viable lung may be conceptualized as being smaller rather than stiff. Although
the total lung compliance is reduced, as little as 25% of the lung may be participating in gas exchange.
Those remaining intact lung regions have better compliance and are thus subject to overdistention and
potential air leak complications (eg, pneumothorax) when exposed to excessive inflating pressures.
The net effect is impairment in oxygenation. A widened interstitial space between the alveolus and the
vascular endothelium decreases oxygen-diffusing capacity. Hypoxia arises as a result of the change
described above. Collapsed alveoli result in either low ventilation-perfusion (V/Q) units or a right-to-left
pulmonary shunt. The end result is marked venous admixture, the process whereby deoxygenated blood
passing through the lungs does not absorb sufficient oxygen and causes a relative desaturation of arterial
blood when it mixes with blood that is already oxygenated.
Pulmonary hypertension may also ensue from ARDS. Hypoxia, hypercarbia, and small-vessel thrombosis
combine to elevate pulmonary artery pressures. Persistent pulmonary hypertension can result in
increased right ventricular work, right ventricular dilatation, and, ultimately, left ventricular outflow tract
obstruction secondary to intraventricular septal shifting toward the left ventricle. These changes, in turn,
may decrease cardiac output and further reduce oxygen delivery to vital organs.
Iatrogenic problems may further complicate the patients clinical picture. Oxygen toxicity can be seen with
prolonged FiO2 of greater than 60%, leading to secondary lung injury from oxygen free radical damage. A
high FiO2 (>95%) may also cause absorption atelectasis, further reducing the number of patent alveoli.
Fluid resuscitation may also lead to further alveolar and pulmonary interstitial flooding, with worsening
compliance and oxygenation. An adult, multicenter trial prospectively compared 2 fluid management
strategies and examined the effects on oxygenation and ventilator-free days. The "conservative" fluid
management over the first 7 days resulted in a net fluid balance of -136 mL, compared with "liberal" fluid
management of 6,993 mL. The study demonstrated that the conservative fluid management strategy
resulted in an increased number of ventilator-free days, improved oxygenation index, and decreased ICU
length of stay.
[7]

This was reproduced in a pediatric patient population in a retrospective cohort study on 168 patients
hospitalized with respiratory failure between 2007 and 2010. A significant association was found between
increasing net positive fluid balance and decreasing ventilator-free days by the third day after meeting
criteria for acute lung injury. The mean cumulative fluid balance was found to be approximately 85 mL/kg
at that time.
[8]

Another pediatric retrospective chart review found associations between peak fluid overload percent and
severe fluid overload of 15% or more with longer duration of mechanical ventilation as well as increased
pediatric ICU and total hospital length of stays.
[9]