neonatal lung injury

Neonatal lung injuryAntonio Souto

[email protected]édico coordenador

Unidade de Medicina Intensiva PediátricaUnidade de Medicina Intensiva Neonatal

Hospital Padre Albino

Professor de Pediatria nível II Faculdades Integradas Padre Albino

Catanduva / SP

Dr. Antonio Souto [email protected] 2013

UTI Pediátrica & Neonatal Hospital Padre Albino

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

It is surprising that mechanical ventilation is not more harmful



The lungs of the very preterm infant

•Structurally immature and are often surfactant-deficient, 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



•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



•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, intraventricularhemorrhage, and retinopathy of prematurity

Several studies show that optimizing lung recruitment reduces lung inflammation,

improves surfactant function, and decreases lung injury.



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



•High tidal volume and zero EEPSevere 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 protectiv e.Both end-expiratory and end-inspiratory lung volumes are important.



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



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



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



Preterm infantPreterm infantPreterm infantPreterm 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 TV of 10 TV of 10 TV of 10 mLmLmLmL/kg delivered may be equivalent to /kg delivered may be equivalent to /kg delivered may be equivalent to /kg delivered may be equivalent to

20 to 30 20 to 30 20 to 30 20 to 30 mLmLmLmL/kg and will result in volutrauma/kg and will result in volutrauma/kg and will result in volutrauma/kg and will result in volutrauma



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



Lung Injury

Oxygen toxicity

Reactive oxygen metabolites

•Overwhelm the antioxidant system•Oxidize enzymes•Inhibit protein and DNA synthesis•Decrease surfactant synthesis•Cause lipid peroxidation.



Lung Injury

Oxygen toxicity

Prolonged Prolonged Prolonged Prolonged hyperoxiahyperoxiahyperoxiahyperoxia initiates a lung injury initiates a lung injury initiates a lung injury initiates a lung injury sequence that can lead to inflammation, diffuse sequence that can lead to inflammation, diffuse sequence that can lead to inflammation, diffuse sequence that can lead to inflammation, diffuse

alveolar damage, progressive pulmonary alveolar damage, progressive pulmonary alveolar damage, progressive pulmonary alveolar damage, progressive pulmonary dysfunction, and death.dysfunction, and death.dysfunction, and death.dysfunction, and death.



Cytokines and biotrauma in ventilator-induced lunginjury

Pulmonary and systemic inflammatory responses to acute lung injury

Significant potential exists for the lungs to Significant potential exists for the lungs to Significant potential exists for the lungs to Significant potential exists for the lungs to interact with, and contribute to, the interact with, and contribute to, the interact with, and contribute to, the interact with, and contribute to, the

circulating pool of inflammatory cells.circulating pool of inflammatory cells.circulating pool of inflammatory cells.circulating pool of inflammatory cells.



Mechanical ventilation affects the numbers of inflammatory cells and the expression of soluble mediators within the lungs

•Increased lung neutrophil accumulation

•Increased inflammatory mediators bronchoalveolarlavage

•Increased expression of tumor necrosis factor–[alpha] by alveolar macrophages

Manifestations of lung injury were almost completely Manifestations of lung injury were almost completely Manifestations of lung injury were almost completely Manifestations of lung injury were almost completely abrogated in granulocyteabrogated in granulocyteabrogated in granulocyteabrogated in granulocyte----depleted rabbitsdepleted rabbitsdepleted rabbitsdepleted rabbits



Injure the alveolarInjure the alveolarInjure the alveolarInjure the alveolar----capillary barriercapillary barriercapillary barriercapillary 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.



Cytokines are likely to play a role in thevarious interrelated processes that lead to VILI and other MV-related complications,

such as MODS and possibly ventilatorassociated pneumonia.



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 area s and to normalize FRC



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



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



Changes in lung volume are dependent on regional lung compliance

Optimal is the tidal volume that creates a Optimal is the tidal volume that creates a Optimal is the tidal volume that creates a Optimal is the tidal volume that creates a homogeneous delivery of each breath to the homogeneous delivery of each breath to the homogeneous delivery of each breath to the homogeneous delivery of each breath to the open lung units without creating volutraumaopen lung units without creating volutraumaopen lung units without creating volutraumaopen 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



How might we measure optimal lung volume?

•Thoracic expansibility

•X ray

•PaCO2/Minute volume (RR/TV)

•PaO2/FiO2/PEEP•Heart frequency



•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 twoOptimal is somewhere between the twoOptimal is somewhere between the twoOptimal is somewhere between the two



How do we safely establish

and normalize

FRC in neonates

with immature and atelectatic prone lungs?



What can we do clinically to prevent What can we do clinically to prevent What can we do clinically to prevent What can we do clinically to prevent atelectraumaatelectraumaatelectraumaatelectrauma????

•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.



CPAP

Pediatrics 2000;105:1194Pediatrics 2000;105:1194Pediatrics 2000;105:1194Pediatrics 2000;105:1194----201201201201

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



When to provide mechanical ventilation?When to provide mechanical ventilation?When to provide mechanical ventilation?When to provide mechanical ventilation?

A problem is the potential risks of waiting to A problem is the potential risks of waiting to A problem is the potential risks of waiting to A problem is the potential risks of waiting to interveneinterveneinterveneintervene

•delaying the “appropriate” use of surfactant

Well-designed trials in which CPAP is compared with early intubation are needed



SurfactantSurfactantSurfactantSurfactant

•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



What is the correct target PaCOWhat is the correct target PaCOWhat is the correct target PaCOWhat is the correct target PaCO2222????

•Moderate hypercarbia protects the brain from hypoxic-ischemic 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



Thus, a Thus, a Thus, a Thus, a ““““normalnormalnormalnormal”””” PaCOPaCOPaCOPaCO2222 value should value should value should value should remain the target until more data from remain the target until more data from remain the target until more data from remain the target until more data from

human studies are availablehuman studies are availablehuman studies are availablehuman studies are available



Preventing oxygenPreventing oxygenPreventing oxygenPreventing oxygen----induced lung injuryinduced lung injuryinduced lung injuryinduced lung injurySTOPSTOPSTOPSTOP----ROP Study Group. Supplemental Therapeutic Oxygen for ROP Study Group. Supplemental Therapeutic Oxygen for ROP Study Group. Supplemental Therapeutic Oxygen for ROP Study Group. Supplemental Therapeutic Oxygen for PrethresholdPrethresholdPrethresholdPrethreshold Retinopathy Of Prematurity (STOPRetinopathy Of Prematurity (STOPRetinopathy Of Prematurity (STOPRetinopathy Of Prematurity (STOP----ROP), a ROP), a ROP), a ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics randomized, controlled trial. I: primary outcomes. Pediatrics randomized, controlled trial. I: primary outcomes. Pediatrics randomized, controlled trial. I: primary outcomes. Pediatrics 2000;105:2952000;105:2952000;105:2952000;105:295----310310310310

•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 8.5% conventional 8.5% conventional 8.5% conventional vsvsvsvs 13.2% supplemental13.2% supplemental13.2% supplemental13.2% supplemental



Preventing oxygenPreventing oxygenPreventing oxygenPreventing oxygen----induced lung injuryinduced lung injuryinduced lung injuryinduced lung injuryTin W, Milligan DW, Tin W, Milligan DW, Tin W, Milligan DW, Tin W, Milligan DW, PennefatherPennefatherPennefatherPennefather P, Hey E. Pulse P, Hey E. Pulse P, Hey E. Pulse P, Hey E. Pulse oximetryoximetryoximetryoximetry, severe , severe , severe , severe retinopathy, and outcome at one year in babies of less than 28 wretinopathy, and outcome at one year in babies of less than 28 wretinopathy, and outcome at one year in babies of less than 28 wretinopathy, and outcome at one year in babies of less than 28 weeks eeks eeks eeks gestation. Arch gestation. Arch gestation. Arch gestation. Arch DisDisDisDis Child Fetal Neonatal Ed 2001; 84:F106Child Fetal Neonatal Ed 2001; 84:F106Child Fetal Neonatal Ed 2001; 84:F106Child Fetal Neonatal Ed 2001; 84:F106----F110F110F110F110

•Oxygen for 8 weeks

•saturation of 88% to 98% X saturation of 70% to 90%

•saturation of 88% to 98%saturation of 88% to 98%saturation of 88% to 98%saturation of 88% to 98%

•severe retinopathy 5 times more often

•more often developed chronic lung disease



Keep in

your mind If these strategic principles If these strategic principles If these strategic principles If these strategic principles are followed, we can reduce are followed, we can reduce are followed, we can reduce are followed, we can reduce the pulmonary and systemic the pulmonary and systemic the pulmonary and systemic the pulmonary and systemic

inflammatory changes inflammatory changes inflammatory changes inflammatory changes associated with ventilatorassociated with ventilatorassociated with ventilatorassociated with ventilator----

induced lung injury and induced lung injury and induced lung injury and induced lung injury and hopefully promote better hopefully promote better hopefully promote better hopefully promote better

longlonglonglong----term health.term health.term health.term health.

neonatal lung injury

Health & Medicine

lung injury sequence

lung mechanics

lung inflation

lung inflammationdr

lung injurydr

ventilatorinduced lung

lung recruitment strategy

antonio soutohospital