Neonatal lung injury

Neonatal lung injury
Antonio Souto
acasouto@bol.com.br
Médico coordenador
Unidade de Medicina Intensiva Pediátrica
Unidade de Medicina Intensiva Neonatal
Hospital Padre Albino
Professor de Pediatria nível II
Faculdades Integradas Padre Albino
Catanduva / SP

UTI Pediátrica & Neonatal


•30 breaths/min
•Distend the lungs more than 40,000
times per day

It is surprising that mechanical
ventilation is not more harmful
Dr. Antonio Souto

acasouto@terra.com.br

2013



The lungs of the very preterm infant
•Structurally immature and are often surfactantdeficient, fluid-filled, and not supported by a stiff chest
wall
•Antenatal exposure to inflammatory mediators,
surfactant dysfunction, high chest wall compliance,
antioxidant deficiency, infection, and malnutrition
•Increase the susceptibility to lung injury
•Limit the ability to repair the damage

Dr. Antonio Souto


2013



•The process of supporting gas exchange in the very low
birth weight infant may have lifelong consequences
•In the delivery room where we must support a safe
transition from fetal to neonatal life
•Support gas exchange and normalize lung inflation from
the first breath is important

Dr. Antonio Souto


2013



•Specific decisions about respiratory care practice during
the first day of life influence the outcome of a very low
birth weight infant
•Failure to decrease ventilatory support may increase the
risk of developing chronic lung disease, intraventricular
hemorrhage, and retinopathy of prematurity

Several studies show that optimizing lung
recruitment reduces lung inflammation,
improves surfactant function, and decreases
lung injury.
Dr. Antonio Souto


2013



Ventilator pattern influenced the efficacy of
exogenously delivered surfactant

•Loss of FRC (lung de-recruitment)
•increased lung injury
•decreased the efficacy of the surfactant therapy
•IMV + inadequate PEEP will increase lung injury

Dr. Antonio Souto


2013



•High tidal volume and zero EEP
Severe lung injury
Marked increases in circulating tumor necrosis
factor and macrophage inflammatory protein
•Large tidal volumes and low end expiratory lung
volumes
Synergistic increase in lung and serum cytokine
concentrations
•The use of a lung recruitment strategy is protective.
Both end-expiratory and end-inspiratory lung
volumes are important.
Dr. Antonio Souto


2013


Dr. Antonio Souto



2013



Lung Injury
Inadequate alveolar stability and atelectasis
Atelectrauma
•Loss of alveolar recruitment is both a consequence and
a cause of lung injury
•Alveolar units are prone to collapse (ARDS/RDS)
•Recruitment and subsequent “de-recruitment” cause
lung injury
Recruitment of lung volumes protects against
ventilator-induced lung injury and also reduces the
need for high levels of inspired oxygen
Dr. Antonio Souto


2013



Lung Injury
Volutrauma
An important cause of ventilator-induced lung injury is
regional overdistension of alveoli and airways.
Large tidal volume breaths
Damage
•pulmonary capillary endothelium
•alveolar and airway epithelium
•basement membranes

Dr. Antonio Souto


2013



Lung Injury
Volutrauma
Fluid, protein, and blood to leak into the airways, alveoli,
and the lung interstitium
•Interfering with lung mechanics
•Inhibiting surfactant function
•Promoting lung inflammation

Dr. Antonio Souto


2013



Preterm infant
•

Lung immaturity, alveolar atelectasis, and edema
decrease the gas volume

•

Only a small portion of the lung may be recruited and
available for ventilation

TV of 10 mL/kg delivered may be equivalent to
mL/kg
mL/kg
20 to 30 mL/kg and will result in volutrauma

Dr. Antonio Souto


2013



Lung Injury
Oxygen toxicity
Oxygen-induced lung injury
•Overproduction of superoxide, hydrogen peroxide,
and perhydroxyl radicals
•The premature is particularly vulnerable
•Antioxidant systems develop during the last trimester

Dr. Antonio Souto


2013



Lung Injury
Oxygen toxicity
Reactive oxygen metabolites
•Overwhelm the antioxidant system
•Oxidize enzymes
•Inhibit protein and DNA synthesis
•Decrease surfactant synthesis
•Cause lipid peroxidation.

Dr. Antonio Souto


2013



Lung Injury
Oxygen toxicity

Prolonged hyperoxia initiates a lung injury
sequence that can lead to inflammation, diffuse
alveolar damage, progressive pulmonary
dysfunction, and death.

Dr. Antonio Souto


2013



Cytokines and biotrauma in ventilator-induced lung
injury
Pulmonary and systemic inflammatory responses to
acute lung injury

Significant potential exists for the lungs to
interact with, and contribute to, the
circulating pool of inflammatory cells.

Dr. Antonio Souto


2013



Mechanical ventilation affects the numbers of inflammatory
cells and the expression of soluble mediators within the
lungs
•Increased lung neutrophil accumulation
•Increased inflammatory mediators bronchoalveolar
lavage
•Increased expression of tumor necrosis factor–
[alpha] by alveolar macrophages
Manifestations of lung injury were almost completely
abrogated in granulocyte-depleted rabbits
granulocyteDr. Antonio Souto


2013



alveolarInjure the alveolar-capillary barrier
•Efflux of inflammatory mediators into the general
circulation.
•A systemic inflammatory response can also be promoted
by translocation of bacteria and endotoxin from the air
spaces into the circulation.
•Findings in recent human studies in adults show that
ventilatory strategy has an impact on pulmonary and
systemic cytokines and that these changes are associated
with multisystem organ failure.

Dr. Antonio Souto


2013



Cytokines are likely to play a role in the
various interrelated processes that lead to
VILI and other MV-related complications,
such as MODS and possibly ventilator
associated pneumonia.

Dr. Antonio Souto


2013



Strategies to Prevent Lung Injuries
What is the definition of optimal lung volume?

•Lung disease or lung injury
•FRC is decreased
•Generally the dependent areas, is collapsed
•Inhomogeneous pattern of inflation

A goal of respiratory support is to open these areas
and to normalize FRC
Dr. Antonio Souto


2013



Optimal lung inflation

Lung volume at which the recruitable lung is open but not
overinflated
•intrapulmonary shunt is decreased
•lung volume effects on cardiac output are minimized
•oxygen delivery is optimized

Dr. Antonio Souto


2013



Lung is recruited
•Surfactant and alveolar interdependence keep it
inflated
•The pressure to open the lung is higher than the
pressure needed to keep it open
•MAP or EEP can be decreased not below the closing
pressure of the majority of the alveoli

Dr. Antonio Souto


2013



Changes in lung volume are dependent on regional lung
compliance

Optimal is the tidal volume that creates a
homogeneous delivery of each breath to the
open lung units without creating volutrauma
•The most important volume to optimize is FRC
•An open lung allows more uniform distribution of each tidal
volume breath and reduces the potential for volutrauma
Dr. Antonio Souto


2013



How might we measure optimal lung volume?

•Thoracic expansibility
•X ray
•PaCO2/Minute volume (RR/TV)
•PaO2/FiO2/PEEP
•Heart frequency

Dr. Antonio Souto


2013



•Low lung volume
•Chest radiograph showing atelectasis along with a
PaO2/PAO2 ratio demonstrating poor oxygenation
•Lung volume is too high.
•Chest radiograph shows lung hyperinflation and there
are clinical signs of decreased cardiac output

Optimal is somewhere between the two

Dr. Antonio Souto


2013



How do we safely establish
and normalize
FRC in neonates
with immature and atelectatic prone lungs?

Dr. Antonio Souto


2013



atelectrauma?
What can we do clinically to prevent atelectrauma?
•Three techniques:
•Nasal SIMV/Continuous positive airway pressure
(CPAP)
•Exogenous surfactant therapy
•Lung recruitment strategy
Strategies to improve lung recruitment include prone
positioning and sustained lung-inflation maneuvers.
Dr. Antonio Souto


2013



CPAP
2000;105:1194Pediatrics 2000;105:1194-201

•Comparing nurseries that more commonly use assisted
ventilation with nurseries that use CPAP in the initial
treatment of very low birth weight infants

•most of the increased risk of chronic lung disease
most
was explained “simply by the initiation of
ventilation.”
mechanical ventilation.”
•Practice differences influence outcome

Dr. Antonio Souto


2013



When to provide mechanical ventilation?

A problem is the potential risks of waiting to
intervene
•delaying the “appropriate” use of surfactant
Well-designed trials in which CPAP is compared with
early intubation are needed

Dr. Antonio Souto


2013



Surfactant
•When used early, decreases lung injury
•Within minutes oxygenation improves in most infants
•Increase in FRC
•Improved ventilation-perfusion matching
•Decrease in intrapulmonary shunt
•Stabilize recruited lung volume and prevents atelectasis

Dr. Antonio Souto


2013



What is the correct target PaCO2?
•Moderate hypercarbia protects the brain from hypoxicischemic injury
•Hypocarbia increases the injury
•Hypercapnic acidosis can protect the lung from acute injury
However
•Hypercarbia increases cerebral blood flow
•Decreases systemic pH
•In animals, increase in retinopathy
Dr. Antonio Souto


2013



Thus, a “normal” PaCO2 value should
normal”
remain the target until more data from
human studies are available

Dr. Antonio Souto


2013



oxygenPreventing oxygen-induced lung injury
STOP-ROP Study Group. Supplemental Therapeutic Oxygen for
STOPPrethreshold Retinopathy Of Prematurity (STOP-ROP), a
(STOPrandomized, controlled trial. I: primary outcomes. Pediatrics
2000;105:2952000;105:295-310

•Neonates
•conventional oxygen pulse oximetry at 89% to 94%
•supplemental pulse oximetry at 96% to 99%
•Pneumonia, exacerbations of chronic lung disease, or
both
•8.5% conventional vs 13.2% supplemental
8.5%

Dr. Antonio Souto


2013



oxygenPreventing oxygen-induced lung injury
oximetry,
Tin W, Milligan DW, Pennefather P, Hey E. Pulse oximetry, severe
weeks
retinopathy, and outcome at one year in babies of less than 28 weeks
84:F106gestation. Arch Dis Child Fetal Neonatal Ed 2001; 84:F106-F110

•Oxygen for 8 weeks
•saturation of 88% to 98% X saturation of 70% to 90%
•saturation of 88% to 98%
saturation
•severe retinopathy 5 times more often
•more often developed chronic lung disease

Dr. Antonio Souto


2013



Keep in
your mind

Dr. Antonio Souto

If these strategic principles
are followed, we can reduce
the pulmonary and systemic
inflammatory changes
ventilatorassociated with ventilatorinduced lung injury and
hopefully promote better
longlong-term health.

2013

Neonatal lung injury

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