By J. Brady Scott, RRT-ACCS, and Michael Gentile, RRT, FAARC
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a variety of critical illnesses characterized by diffuse damage to the alveolar-capillary lung structures with hypoxemia and noncardiogenic pulmonary edema. ARDS is a global public health issue with significant morbidity and mortality that may be seen in both medical and surgical patients. The American-European Consensus Conference (AECC) defined ARDS in 1994 as: acute in onset, chest x-ray findings of bilateral infiltrates on frontal chest radiograph, no clinical evidence of left atrial hypertension (pulmonary capillary wedge pressure <18), and a Pao2/Fio2 ratio ?200 (?300 for ALI).
This definition has worked at least well enough to allow for a large amount of research to be conducted on ARDS. However, despite being used somewhat successfully, the definition still lacks sufficient detail and is considered by some to be rather unclear. The term “acute” has been thought by some to be vague, while chest radiograph results of “bilateral infiltrates” may allow for intraobserver variability, and positive end-expiratory pressure (PEEP) may affect Pao2/Fio2 ratios. As a result, the definition was revised recently.
Some changes to the AECC definition by the ARDS task force (termed the Berlin definition) was to redefine “acute” as ?7 days from the predisposing clinical insult, and radiographic evidence now includes bilateral opacities on radiograph or computed tomography scan not fully explained by effusion, atelectasis, or nodules. In addition to these revisions, the pulmonary capillary wedge pressure cutoff values that distinguish ARDS from cardiogenic edema were eliminated, and the term “acute lung injury” was replaced with three levels of ARDS severity based on Pao2/Fio2 measured with at least 5 cm H2O of applied PEEP.1,2
To best understand the treatment of ARDS, it is important to understand the pathophysiology. Initially, the exudative phase begins as diffuse damage occurs in the lungs. During this phase, an influx of inflammatory cells cross into the interstitium and the alveolar spaces become engulfed with material called hyaline membranes. These hyaline membranes are made up of cellular debris and condensed plasma proteins. ARDS may present with shortness of breath, tachypnea, and hypoxemia during this stage that may mimic respiratory failure due to cardiogenic pulmonary edema. The respiratory failure may be due to the accrual of the protein-rich fluid in the distal airspaces. Respiratory distress also may be attributed to decrease in surfactant production by the type II alveolar cells.
Another phase of ARDS progression is considered the proliferative or fibroproliferative phase. This happens after the inflammatory injury has occurred and the events that set off the process are controlled. A significant increase in type II alveolar cells and fibroblasts occurs along with the thickening of alveolar capillaries. The fibroblasts mediate the formation of intra-alveolar and interstitial fibrosis.3 The degree of pulmonary compromise in patients who survive ARDS is related to the extent of the fibrosis that occurs. The pathophysiology of ARDS is quite complex and can result in severe respiratory system failure.
The prevalence of ARDS represents only about 5% of hospitalized, mechanically ventilated patients.2 Most cases are considered moderate to severe, and approximately one-third of patients with mild ARDS will continue on into the moderate to severe category. Although the prevalence of the syndrome is relatively low, the mortality rate has been reported to be approximately 40%. The mortality rate varies though with disease severity. While ARDS is often thought of as a respiratory disorder, the majority of patients diagnosed actually die from multisystem organ failure.
Treatment of ALI/ARDS
Management of these critically ill patients with ALI/ARDS involves a systematic approach. The treatment strategy is largely supportive and is designed to prevent further lung injury and treat the underlying cause of the condition. Most patients who are diagnosed with ARDS ultimately require mechanical ventilation. While mechanical ventilation is a life saving modality, it does not come without hazard. Due to the heterogeneity of the disease, mechanical ventilation strategies that incorporate large tidal volumes have been found to be inappropriate. Excessive tidal volumes can lead to hyperinflation and overdistension of the alveoli in the aerated regions of a diseased lung. Hyperinflation of these lung units may result in a very similar pattern of altered alveolar permeability found in ARDS. Because of research from the National Institutes of Health ARDSNet trial, lung-protective strategies with tidal volumes of 6 mL/kg of predicted body weight and plateau pressures of less than 30 cm H2Oare now considered a standard of care.
Despite progress in reducing the rate of mortality over the years, clinicians are still searching for ways to better treat patients who are “failing” conventional mechanical ventilation. Currently, no ventilator modalities show superiority over the others in terms of survival as an outcome. However, some strategies do indeed improve oxygenation and may offer some real promise as more supportive literature is unveiled.
One approach that has gained renewed interest over the last few years is high frequency oscillatory ventilation (HFOV). Many hospitals are using HFOV for patients who are unable to sustain adequate levels of oxygenation despite escalating levels of mechanical ventilatory support.4 The renewed interest in this strategy really seemed to coincide with the 2009 H1N1 epidemic. Interestingly, while HFOV is relatively new in the adult population, it has been used extensively in the neonatal population for the past 20 years.5
High frequency oscillatory ventilation works on the premise of rapid rates and ultrasmall tidal volumes. Mean airway pressure (mPaw) inside the lung is held constant, and gas exchange occurs through a number of mechanisms including bulk convection, cardiac oscillations, Taylor dispersion, pendelluft, asymmetric velocity profiles, and molecular diffusion. Both inhalation and exhalation are active because the diaphragm (which oscillates between 180 and 600 bpm or 3-15 Hz) is actively driven both forwards and backwards. Tidal volumes and ventilation are directly proportional to the delta P and inversely proportional to the frequency. Oxygenation is dependent on adequate mean airway pressure and the fraction of inspired oxygen (Fio2) setting.
In theory, HFOV could be more advantageous than conventional mechanical ventilation due to the smaller delivered tidal volumes and alveolar recruitment. The smaller tidal volumes may be lung protective because of the reduction of alveolar overdistension. Maintaining the mPaw, which in turn prevents alveolar de-recruitment, reduces damage that occurs from the repetitive opening and closing of the alveolus. The ability to maintain a higher mean airway pressure also may improve the overall oxygenation status of the patient. Because of this, Fio2 levels are typically reduced, leading to an avoidance of oxygen toxicity.
While the use of HFOV is widespread, the evidence-based medicine supporting its use in the treatment of ARDS is challenging. There is much debate regarding the timing of this modality. Most experts tend to agree that early initiation of HFOV is likely the best approach. Despite efforts to determine the cause of mortality, none have adequately linked timing of HFOV to mortality after adjusting for other factors.6 Regardless of the lack of clear evidence of timing, ideally this method would be employed well before the lungs were exposed to injurious ventilator settings.
Most investigations regarding HFOV have focused on its use as a rescue therapy for patients failing mechanical ventilation. Early studies such as the Multicenter Oscillatory Ventilation for Acute Respiratory Distress Syndrome Trial (MOAT) showed no real mortality benefit with the use of HFOV versus conventional mechanical ventilation (CV). It can be noted that a trend toward lower mortality did exist within the HFOV group compared to the CV group. An improvement in the Pao2/Fio2 ratio also was found. This study, however, does not compare more contemporary ARDS lung protective strategies and may have overestimated the benefit of HFOV. More recent literature has suggested that HFOV may reduce mortality when compared to CV, is unlikely to harm the patient, and may be as effective as CV in centers with HFOV expertise.7 Unfortunately, these types of trials are difficult to conduct given the severity of disease and preexisting patient conditions affecting survival as an outcome measurement.
Currently, there are two large randomized controlled trials that are being conducted to help determine the mortality benefit of HFOV in ARDS. The OSCILLATE trial will enroll approximately 1,200 adult patients with ARDS. Ventilator settings will be more consistent with the ARDSNet low tidal volume strategy utilizing the 6 ml/kg/IBW approach. Another multicentered, prospective trial comparing the effects of HFOV with CV on mortality in adult ARDS is the OSCAR trial. The trial has ceased and the results will be reported in the near future. Hopefully, these two trials will give us more conclusive evidence on the mortality benefits of HFOV.
The use of high frequency oscillatory ventilation in the treatment of ARDS has increased over recent years. Despite many reports of success, there is still some considerable debate regarding the actual benefits of HFOV versus other lung protective strategies of ventilation. While we wait on more data to evolve, it is reasonable to consider HFOV due to the physiologic rationale and the early small trials that have shown promising results. ?
J. Brady Scott, RRT-ACCS, is the clinical education coordinator for respiratory care services at Rush University Medical Center, Chicago; and Michael Gentile, RRT, FAARC, is an associate in research at Duke University Medical Center, Durham, NC. For further information, contact [email protected].
1. The ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307(23):2526-2533.
2. Walkey AJ, Summer R, Ho V, Alkana P. Acute respiratory distress syndrome: epidemiology and management approaches. Clin Epidemiol. 2012:4 159-169.
3. Tomashefski JF Jr. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med. 2000;21:435-466.
4. Pipeling MR, Fan E. Therapies for refractory hypoxemia in acute respiratory distress syndrome. JAMA. 2010;304:2521-2527.
5. Ali S, Ferguson ND. High-frequency oscillatory ventilation in ALI/ARDS. Crit Care Clin. 2011;27:487-499.
6. Bollen C, Uiterwall C, Van Vught A. Systematic review of determinants of mortality in high frequency oscillatory ventilation in acute respiratory distress syndrome. Crit Care. 2006;10(1):R34.
7. Ip T, Mehta S. The role of high-frequency oscillatory ventilation in the treatment of acute respiratory failure in adults. Curr Opin Crit Care. 2012;18:70-79.