Intensive Care Doctor-Community

"...ALI and its more severe form,...ARDS, are devastating disorders of overwhelming pulmonary inflammation leading to hypoxemia and respiratory failure," write Adrienne G. Randolph, MD, MSc, from Perioperative and Pain Medicine, Children's Hospital and Harvard Medical School in Boston, Massachusetts. "There are detailed overviews of the diagnosis, epidemiology, pathogenesis, and treatment of adults with ALI/ARDS. This concise review is designed to focus on children, highlighting differences between children and adults in the epidemiology, diagnosis, prognosis, and evidence-base for management of pediatric ALI/ARDS."

Criteria for ALI and ARDS Diagnosis

Both in adults and in children, ALI and ARDS are most often diagnosed from criteria proposed by the American European Consensus Conference (AECC), with use of 4 clinical parameters. These parameters are (1) acute onset, (2) severe arterial hypoxemia not responding to use of inhaled oxygen alone (PaO₂/FIO₂ ratio ≤ 200 torr [≤ — kPa] for ARDS and PaO₂/FIO₂ ratio ≤ 300 torr [≤ — kPa] for ALI), (3) chest radiography showing bilateral infiltrates suggestive of diffuse pulmonary inflammation, and (4) absence of left atrial hypertension.

Although lung histology criteria for ARDS include evidence of diffuse alveolar damage, lung biopsy is seldom performed in children with ALI and ARDS. Children diagnosed by AECC criteria have prolonged duration of respiratory failure, requiring mechanical ventilation for 10 to 16 days, on average, and overall mortality rates are 10% to 40%.

The goal of this review was to offer clinicians a summary of the pertinent literature concerning pediatric management of ALI/ARDS by searching PubMed for clinical trials and performing a selected literature review of other relevant studies describing the epidemiology and diagnosis of ALI/ARDS.

Adults and children share common risk factors and pathophysiology of ALI/ARDS, with infection, particularly in the lower respiratory tract, being the most common trigger. In children, ALI and ARDS are associated with high morbidity rates, high death rates, and high healthcare costs. Reported population estimates suggest that the annual incidence of ALI in US children is 2500 to 9000, resulting in or contributing to 500 to 2000 deaths.

Clinical trials of ALI/ARDS are difficult to perform in children because of lower mortality rates as well as a relatively lower incidence of ALI/ARDS in this age group. The review author therefore relied, to some extent, on expert opinion.

Recommended Interventions

Expert opinion suggests that the following interventions be recommended:

1. Tidal volumes of more than 10-mL/kg body weight should be avoided.

2. Recommended ventilation parameters are plateau pressure of less than 30 centimeters H₂O, arterial pH of 7.35 to 7.45, and PaO₂ of 60 to 80 torr (— to — kPa; SpO₂ > 90%).

3. Supplementary pharmacotherapy should include sedation, analgesia, and stress ulcer prophylaxis.

4. In patients who are unstable because of shock or profound hypoxia, a 10-g/dL hemoglobin threshold is recommended for packed red blood cell transfusion. Once profound hypoxia and shock have resolved, evidence supports lowering the hemoglobin transfusion threshold to 7 g/dL.

"Untreated infection, necrosis of tissue, pancreatitis, and other persistent triggers of the inflammatory cascade will lead to unrelenting escalation of ARDS," Dr. Randolph writes. "Identification of the ARDS trigger source and achievement of source control are essential to optimize clinical outcomes. Because sepsis is commonly the trigger for ALI, early antibiotic therapy is recommended in those suspected of being infected."

Other Possible Treatments

For children with ALI/ARDS, there are no clear guidelines for beginning endotracheal intubation and ventilator support, except for loss of consciousness and inability to protect the airway. When intubation is needed in children, this should be performed by those with sufficient experience in intubating children, using appropriately sized equipment and endotracheal tubes. Delivery of adequate positive end-expiratory pressure when pulmonary compliance is low may best be achieved with use of cuffed endotracheal tubes.

Based on evidence from pediatric trials, promising treatments of pediatric ALI/ARDS include use of endotracheal surfactant; high-frequency oscillatory ventilation; noninvasive ventilation; and, as a rescue treatment, use of extracorporeal membrane oxygenation therapy.

Evidence from adult studies suggests that use of corticosteroids to treat lung inflammation and fibrosis, use of 4- to 6-mL/kg tidal volumes, and restrictive fluid management may be helpful. However, fluids should only be restricted once children have recovered sufficiently from septic shock.

In adults and children with respiratory failure and ALI/ARDS after hematopoietic stem cell transplant, mortality rate is 75% or more. Interventions for which potential benefits may outweigh the risks include continuous venovenous hemofiltration, bronchoalveolar lavage, etanercept, and/or lung biopsy in selected cases to identify undiagnosed, treatable conditions.

Treatments that should be studied further before recommending their use in children with ALI or ARDS include prone positioning, bronchodilator therapy, inhaled nitric oxide, tight glycemic control, and oxygen delivered by high-flow nasal cannula.

Treatment goals for management of ALI/ARDS in children include reducing mortality and morbidity rates, hastening recovery, and optimizing long-term cognitive and respiratory function.

"It is important to minimize profound hypoxia that leads to cell death and is damaging to the developing brain, and to minimize secondary damage to the injured lung and other organ systems that could prolong recovery," Dr. Randolph concludes. "In contrast to adults, severity of hypoxia at presentation is a fairly strong predictor of mortality in children with ALI/ARDS....Multiple organ failure is also a consistent mortality predictor in children with ALI/ARDS."

Dr. Randolph has consulted for Discovery Laboratories and has also served as a scientific advisory board member for a clinical trial of lucinactant.