Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is frequently regarded as one of the most difficult patient populations for a clinician to handle, although accounting for a small proportion of all pediatric ICU patients. ARDS is a type of acute lung injury caused by a variety of pulmonary (direct lung injury) and extrapulmonary (indirect lung injury) causes. Pneumonia (35 percent), aspiration (15 percent), sepsis (13 percent), near-drowning (9 percent), concurrent heart failure (7 percent), and other clinical disorders were the predominant causes in a detailed description of juvenile ARDS (21 percent). Nearly half of these clinical disorders were caused by infectious causes, such as sepsis and pneumonia.

Pulmonary inflammation, alveolar edema, and hypoxic respiratory failure are all hallmarks of ARDS. Inflammatory, proliferative, and fibrotic stages describe the pathophysiology of this disease as it progresses. Since then, doctors treating newborns, kids, adolescents, and adults have faced diagnostic and therapeutic challenges.

Multiple modifications of the ARDS definition for pediatric patients have been made over the years, including the Murray acute lung injury score, the American European Consensus Conference definition, the Delphi Consensus definition, and the Berlin definition. Although these diagnostic criteria were specifically designed for use in the adult population, they were frequently used in pediatric settings until lately.

It's crucial to note that adult-based ARDS classifications may not apply to pediatrics for a number of reasons. Infants and children are more susceptible to severe respiratory injury than adults due to anatomical and physiological changes, which may need a lower intervention cut-off in the pediatric patient. Moreover, compared to teens and adults, younger patients have a higher metabolic requirement and less cardiac capacity. Considering the less widespread use of arterial lines in infants and children, earlier application of adult-based ARDS criteria to pediatrics, with the need to evaluate arterial oxygenation, may have resulted in an underestimating of the prevalence of ARDS in pediatrics. The inclusion of PaO2/FIO2, which can be altered by changes in applied mean airway pressure, as a signal of oxygenation failure is another ongoing problem of adult-based criteria to pediatric clinicians.

To maximize management techniques across the diverse pediatric spectrum extending from infants to teenagers, special provisions are frequently required. The Pediatric Acute Lung Injury Consensus Conference developed a children-specific definition for ARDS in 2015 due to the significant limitations of prior adult-based criteria of ARDS in the pediatric population. Unlike previous adult-based consensus conferences, the Pediatric Acute Lung Injury Consensus Conference provided specific patient care guidelines for pediatric ARDS as well as research needs.

Acute Respiratory Distress Syndrome Definition

In the past, the diagnosis of acute lung injury or ARDS in children was predicted by adult standards established by the American-European Consensus Conference and Berlin definition. Understanding that ARDS in children differs from that in adults, the Pediatric Acute Lung Injury Consensus Conference brought together a worldwide committee of specialists to develop new definitions and recommendations for pediatric acute respiratory distress syndrome. The criteria adopted by the Pediatric Acute Lung Injury Consensus Conference expands the radiographic criterion to encompass any new parenchymal infiltrates. The pediatric ARDS definition also allows for the use of pulse oximetry to prevent underestimating ARDS incidence in children if arterial blood oxygenation measured values are unavailable and SpO2 is less than 97 percent, as well as the use of the oxygenation index (OI) and oxygenation saturation index (OSI) rather than the PaO2/FiO2 (When defining lung disease, the inclusion of an oxygenation index into the definition accommodates for variations in respiratory support.

In two investigations of pediatric patients in the critical care unit, the Pediatric Acute Lung Injury Consensus Conference criteria were recently compared to older classifications. Both trials came to the same conclusion: the revised criteria identified a greater number of pediatric ARDS patients. Patients who met the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric ARDS had a lower overall fatality rate and a lower percentage of severe ARDS and comorbidities when compared to Berlin and American-European Consensus Conference definitions. Even more recently, the largest PARDS study using the Pediatric Acute Lung Injury Consensus Conference definition, the prospective international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study, found that the Pediatric Acute Lung Injury Consensus Conference definition identified more kids as having pediatric ARDS than the Berlin definition in over 700 children. Importantly, using extended criteria to include more patients with milder types of pediatric ARDS could have major repercussions for future outcome measures if they are not stratified by illness severity.

Epidemiology

Respiratory failure is the leading cause of death among children referred to pediatric intensive care units, with ARDS accounting for 1–10 percent of all hospitalizations. The mortality rates in children with ARDS vary widely between studies, owing to a variety of concomitant diseases and causes. Wong et al. identified an aggregated mortality rate of 24 percent in pediatric ARDS, with an overall downward trend in mortality over the last 30 years. This development is likely due to earlier identification and treatment, better ventilation methods, and changes in ICU treatment in general. One study looked at mortality risk based on the severity of pediatric ARDS as defined by the Pediatric Acute Lung Injury Consensus Conference and found a significant, gradual increase in mortality with increasing disease severity (10–15 percent for mild or moderate pediatric ARDS versus 33 percent for severe pediatric ARDS).

Oxygenation index measured 6–12 hours and 24 hours after the beginning of pediatric ARDS was shown to be more reliable in stratifying the degree of lung injury than prognosis at the time of onset. The investigation confirmed this finding, indicating that the severity level of pediatric ARDS at 6 hours was more prognostic of ICU death than the Berlin ARDS severity categories.

Overall, pediatric ARDS mortality has declined in recent decades and is now lower than adult ARDS death, which varies from 35 to 46 percent for mild to severe cases. 18 However, the mortality rate for children with ARDS remains high, and advances in detection, risk stratification, and targeted care will be necessary to further lower the mortality rate.

Acute Respiratory Distress Syndrome Etiology

ARDS has a number of risk factors. ARDS affects around 20 percent of patients who have no known risk factors. Direct lung injury (most commonly due to aspiration of food from the stomach), systemic disorders, and injuries are all possible causes for ARDS. Sepsis is the most frequent risk factor for ARDS.

According to the number of adult reports, the following are key risk factors of the development of ARDS:

Bacteremia
Sepsis
Trauma, with or without pulmonary contusion
Fractures, particularly long bone fractures
Burns
Massive transfusion
Pneumonia
Aspiration

The American-European consensus conference criteria have not been used to study general ARDS various risks in a prospective study. However, older age, female gender, cigarette smoking, and alcohol consumption seem to enhance the incidence of ARDS after an inciting event. Increased severity of the condition, as indicated by a severity score system like the Acute Physiology and Chronic Health Evaluation, increases the likelihood of developing ARDS, regardless of the underlying etiology.

Glavan et al. investigated the link between individual mutations in the FAS gene and acute lung injury susceptibility in a review. Four single nucleotide polymorphisms were found to be linked to greater acute lung injury susceptibility in the study. The significance of FAS in acute lung injury needs to be investigated more.

Acute Respiratory Distress Syndrome Pathophysiology

Diffuse alveolar injury and lung vascular endothelium injury are also linked to ARDS. The early phase is defined as exudative, while the later phase is described as fibroproliferative.

A rise in the permeability of the alveolar-capillary membrane leads to an inflow of fluid into the alveoli in early ARDS. The vascular endothelium and the alveolar epithelial layer create the alveolar-capillary membrane. As a consequence, ARDS could be caused by a variety of insults that harm the vascular endothelium or the alveolar epithelium.

The main location of injury could be the vascular endothelium or the alveolar epithelium. Increased capillary permeability and the influx of protein-rich fluid into the alveolar space ensue from endothelial injury.

The development of pulmonary edema is also aided by injury to the alveolar epithelial tissue. There are two types of alveolar epithelial cells. Type I cells, which account for 90 percent of the alveolar epithelium, are easily damaged. Excess fluid input into the alveoli and slower fluid outflow from the alveolar space are both possible when type I cells are damaged. Type II alveolar epithelial cells are more resistant to damage than Type I alveolar epithelial cells. Type II cells, on the other hand, perform a variety of critical roles, including surfactant synthesis, intracellular transport, and proliferation and differentiation into type l cells following cell damage. Damage to type II cells causes a reduction in surfactant synthesis, which leads to reduced compliance and alveolar collapse. Fibrosis can be caused by interfering with the natural repair mechanisms in the lungs.

Investigations of bronchoalveolar lavage and lung biopsy specimens in early ARDS reveal that neutrophils play a crucial role in the etiology of the disease.

Acute Respiratory Distress Syndrome Symptoms

The onset of acute breathlessness and hypoxemia within hours to days of an inciting event, such as accident, sepsis, drug overdose, massive transfusion, acute pancreatitis, or aspiration, is known as acute respiratory distress syndrome (ARDS). In many situations, the precipitating incident is evident; but, in others such as drug overdose, it may be more difficult to identify.

Patients with ARDS are generally extremely unwell, with multisystem organ damage, and may be unable to supply history information. The disease usually develops within 1 to 2 days of the inciting event, though it might take up to a few days in exceptional cases.

Patients with acute lung impairment experience dyspnea when they exert themselves at first. This quickly evolves to severe breathlessness at rest, trouble breathing, panic, restlessness, and the demand for higher and higher oxygen levels in the lungs.

Patients at Risk of Pediatric ARDS

The inclusion of the diagnosis of patients at risk for pediatric ARDS was one of the changes offered in the Pediatric Acute Lung Injury Consensus Conference definitions. The age, timeline, edema source, and chest radiography criteria are all the same as in the primary definition; the only difference is in the oxygenation criterion. FiO2 40 percent must keep saturations of 88-97 percent for non-invasive mechanical ventilation patients on continuous positive airway pressure (CPAP) or bilevel positive airway pressure with a nasal mask. A minimum oxygen supply should be delivered to patients using an oxygen mask, nasal cannula, or high-flow nasal cannula to sustain an oxygen saturation of 88-97 percent.

The minimum flow is determined by age: 2 L/min for children under the age of one year, 4 L/min for children aged one to five years, 6 L/min for children aged five to ten years, and 8 L/min for children over ten years. The oxygen supply needed to maintain oxygen saturations higher than 88 percent, but with oxygenation index 4 and oxygen saturation index 5, is the criterion for patients who are at risk for invasive respiratory support.

Acute Respiratory Distress Syndrome Treatment

General Principles

The challenge is identifying the vulnerable population and immediately stratifying them. There is no specific therapy for the inflammatory process or alveolar-epithelial damage. The key to managing PARDS patients is to treat the underlying cause while lung tissue recovers.

Intensivists have been able to increase the overall survival of children with this syndrome by better understanding their ventilatory care. The key to successful care is to avoid causing iatrogenic lung damage. In the present care of pediatric ARDS, this idea is the most important. Mechanical ventilation is linked to a variety of lung injuries, and criteria must be defined to prevent these injuries from recurring and allow for alveolar healing.

Atelectrauma: patients with a low PEEP will see a decrease in alveolar recruitment. These individuals will have alveoli that collapse and distend continuously, resulting in a loss of surfactant and additional collapse. The forced opening of collapsed alveoli, similar to volutrauma, will cause greater inflammation.
Volutrauma: a pulmonary injury caused by a large tidal volume. According to the pulmonary area, overdistension of the alveoli causes inflammation. The pressure it puts on the lungs' many histological layers causes an inflammatory cascade comparable to that seen in children with ARDS.
Barotrauma: the pulmonary lesion is caused by high ventilatory pressures (peak and plateau pressures > 35 cmH2O), which causes alveolar wall breakdown. Pneumothorax and emphysematous lesions, which decrease the gas exchange area, are common in these patients. Patients with air leak conditions as a result of a pneumothorax are extremely difficult to treat.

Mechanical Ventilation

The medical team's experience and the manufacture of ventilators can guide the approach and style of ventilation. Although the synchronized intermittent mandatory ventilation mode with pressure regulator has several benefits, no research has recommended only one mode. Parameters should be employed in any of the specified modes to retain the concept of open lung ventilation. To prevent lung overdistension and additional injury, the open lung and permissive hypercapnia technique is recommended. Except in situations of increased intracranial pressure, pulmonary hypertension, congenital heart defects, hemodynamic instability, and ventricular failure, a pH of 7.15-7.30 can be used as a goal. In children with ARDS, the goal of mechanical ventilation is to preserve the lungs rather than to delay lung damage.

All patients with ARDS need mechanical ventilation, which improves oxygenation while also lowering oxygen demand by relaxing respiratory muscles. The following are a number of the objectives:

Alveolar pressures at the plateau are less than 30 cm H2O.
The tidal volume to prevent further lung injury, use 6 mL/kg predicted body weight.
To avoid oxygen toxicity, keep FIO2 as low as feasible while maintaining adequate oxygen saturation.

PEEP and NIPPV

positive end-expiratory pressure (PEEP) should be kept high enough to keep alveoli inflated and reduce FIO2 until a plateau pressure of 28 to 30 cm H2O is achieved. The use of greater PEEP is most likely to minimize death in patients with moderate to severe ARDS.

Noninvasive positive-pressure ventilation (NIPPV) can help with ARDS sometimes. In comparison to the therapy of cardiogenic pulmonary edema, however, larger levels of support for an extended period of time are frequently required, and Expiratory Positive Airway Pressure of 8 to 12 cm H2O is frequently needed to maintain appropriate oxygenation. To achieve this expiratory pressure, inspiratory pressures of more than 18 to 20 cm H2O are required, which are inadequately tolerated; having sufficient seal becomes challenging, the mask becomes more uncomfortable, and skin injury and gastric dilatation may occur. Furthermore, NIPPV-treated patients who require intubation later have often proceeded to a more advanced state than those who were intubated earlier; hence, significant desaturation can occur during intubation. NIPPV requires close monitoring and cautious selection of patients.

Prone Positioning

On the efficacy of prone positioning for ARDS, adult and pediatric data differ. Curley et al investigated 102 ventilated pediatric participants with early acute lung injury that looked into the role of prone positioning. After a supine-to-prone shift, 90 percent of prone patients demonstrated improvements in oxygenation, as defined by a 20 mm Hg rise in PaO2/FIO2 or a 10 percent decrease in oxygenation index. The trial, however, was discontinued due to inefficiency at a planned midpoint analysis. Despite the fact that prone position proved to be a safe procedure, there were no changes in the primary outcome factor of ventilator-free days or any of the secondary outcome indicators.

The adult PROSEVA trial, on the other hand, showed that people with severe ARDS had a better chance of surviving. There are several significant discrepancies between Curley et al pediatric prone trial and PROSEVA. Curley et al included a diverse group of participants with varying degrees of lung impairment, whereas PROSEVA concentrated on severe ARDS. In addition, when ARDS progressed and oxygenation deteriorated, the pediatric trial dictated the administration of HFOV. This could possibly have been a large confounding factor, given the current ambiguity about the importance of oscillation. As a result, the relevance of the prone position in pediatric ARDS is unknown, and more research is needed.

Acute Respiratory Distress Syndrome Prognosis

Most studies reported a 40-70 percent mortality rate for ARDS until the nineties. In the nineties, however, two investigations, one from a large community hospital in Seattle and the other from the United Kingdom, revealed substantially lower fatality rates, in the 30-40 percent range. Greater understanding and management of sepsis, recent modifications within the use of mechanical ventilation, and better general supportive therapy of severely ill patients could all be risk factors in the higher survival rates.

Although the present success of mechanical ventilation using decreased tidal volumes may indicate a function for lung injury as a primary etiology of mortality in ARDS patients, most deaths are due to sepsis or multi-organ dysfunction rather than a primary pulmonary etiology.

The risk of death from ARDS rises with age. In a study conducted in King County, Washington, patients aged 15 to 19 years old had mortality rates of 24 percent.

The PaO2/FiO2 ratio and other oxygenation and ventilation indicators, such as the PaO2/FiO2 ratio, may be used to interpret the outcome or risk of mortality. One multicenter study including 50 countries demonstrated a link between ARDS severity and inpatient mortality: 35 percent for mild ARDS, 40 percent for intermediate ARDS, and 46 percent for severe ARDS.

In ARDS patients, peripheral blood concentrations of decoy receptor (DcR3), a soluble peptide with immunomodulatory properties, predict 4-week death. Plasma DcR3 values were the only indicator that discriminates survivors from non-survivors at all time periods in week 1 of ARDS in research comparing DcR3, soluble triggering receptor expressed on myeloid cell, TNF-alpha, and IL-6 in ARDS cases. Regardless of APACHE II scores, non-survivors had greater DcR3 concentrations than survivors, and death was increased in individuals with higher DcR3 values.

There is a significant amount of morbidity. Patients with ARDS are more likely to be in the hospital for longer periods of time, and they are more prone to develop nosocomial infections, particularly ventilator-associated pneumonia. Furthermore, patients frequently experience severe weight loss and muscle weakness, and functional disability can last for months following discharge from the hospital.

Severe disease and a long period of mechanical ventilation are both indicators of permanent pulmonary function deficits. For years after recovery, ARDS survivors suffer a considerable functional disability.

Conclusion

Despite years of research and experience handling pediatric ARDS patients, clear data is still lacking, particularly in terms of clinical care. Despite the fact that the Pediatric Acute Lung Injury Consensus Conference has offered the pediatric community a standardized description for infants, children, and adolescents with ARDS, researchers must still implement the proposed criteria and further correspond severity categorization with results. Until clear pediatric data becomes available, current guidelines on pediatric ARDS diagnosis, risk stratification, and treatment will mainly rely on expert judgment and extrapolation of neonatal and adult evidence.