EVIDENCE-BASED CRITICAL CARE PRACTICES

Low Tidal Volume Mechanical Ventilation in Acute Lung Injury and the Acute Respiratory Distress Syndrome

ICUs were first developed to manage patients with acute respiratory failure (ARF) from polio. Since then, management of patients with ARF has been revolutionized by the development of modern mechanical ventilators. ARDS in adults was first described in 1967 by Ashbaugh and coworkers.^[14] They described 12 patients with acute respiratory distress, cyanosis refractory to oxygen therapy, decreased lung compliance, and diffuse bilateral infiltrates on chest radiograph. Because this initial definition lacked specific criteria that could be used to identify patients for research, the American-European Consensus Conference Committee recommended new definitions in 1994.^[15] The consensus definition included the following:

1. Acute onset
2. Bilateral infiltrates on chest radiography
3. Pulmonary artery wedge pressure ≤18 mm Hg or the absence of clinical evidence of left atrial hypertension

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4. PaO₂ :FIO₂ ≤300 for acute lung injury (ALI) or PaO₂ :FIO₂ ≤200 for ARDS

The treatment for ALI or ARDS is primarily supportive with mechanical ventilation, which allows time for treatment of the underlying cause of lung injury and for natural healing.^[17] Until recently, most studies of ALI or ARDS reported a mortality rate of 40% to 60%, with death attributed to sepsis or multiorgan failure rather than primary respiratory causes.^{[18] [19] [20]} Several clinical trials have addressed one of the hallmarks of ALI or ARDS—decreased lung compliance. Traditionally, tidal volumes of 10 to 15 mL/kg were used to mechanically ventilate these patients. The basis for use of these large tidal volumes was twofold. Patients with ARDS demonstrate significant atelectasis on chest radiograph or computed tonographic scan, and when larger tidal volumes are applied, oxygenation often improves. However, the histopathology of ARDS shows heterogeneous infiltration of the lung, with atelectasis and alveolar flooding primarily in the gravity-dependent areas. Many areas of the lung remain relatively uninvolved. When the lung is mechanically ventilated, tidal volume is distributed into the lung according to regional compliance. This may result in regional overinflation and lung injury. In animal models of ALI, large tidal volumes lead to elevated airway pressures, increased pulmonary vascular permeability, acute inflammation, alveolar hemorrhage, intrapulmonary shunt, and diffuse radiographic infiltrates.^{[21] [22]} Based on these studies, it was postulated that large tidal volumes delivered to patients would overdistend uninjured alveoli, promote further lung injury, inhibit resolution of the existing lung injury, and contribute to multiorgan failure.^[23] These concerns led to a number of clinical trials searching for a "protective" ventilatory strategy that could reduce alveolar overdistention and increase recruitment of atelectatic regions of the lung, a so-called open lung approach.

Two early observational studies examined low tidal volume ventilation for patients with ALI or ARDS.^{[24] [25]} Mortality was comparable for the low tidal volume with permissive hypercapnia group compared with historical controls. When Amato and coworkers^[26] employed a protective ventilatory strategy using low tidal volume and higher levels of positive end-expiratory pressure, the mortality rate was reduced from 71% for the control group to 38% for the protective ventilation group. However, three small, prospective, randomized trials of traditional versus low tidal volume ventilation in patients with ALI or ARDS did not demonstrate any beneficial effects.^{[27] [28] [29]}

The definitive study on protective mechanical ventilation was reported in 2000 by the National Institutes of Health (NIH) ARDS network.^[9] In this prospective study of patients with ALI, the mortality rate was reduced from 40% for patients receiving low tidal volume ventilation of 12 mL/kg to 31% for patients receiving 6 mL/kg. The low tidal volume group also had more ventilator-free and organ failure-free days than the higher tidal volume group.^[9] Several reasons have been postulated for the discrepancy between this study and the prior inconclusive studies.^[30] First, the NIH study may have been better able to show a difference because it employed lower tidal volumes than the other studies. Second, the NIH study allowed for treatment of respiratory acidosis with high respiratory rates or with sodium bicarbonate. Treatment of respiratory acidosis may have prevented deleterious effects. Third, the NIH study enrolled 861 patients, which was by far the largest study, increasing the statistical power to find a positive effect of the low tidal volume ventilation.

In a second study using the same patient database, Eisner and associates^[31] found there was no evidence that the efficacy of the low tidal volume strategy varied according to the clinical cause of ARDS. Although the mortality rate was highest (43%) for patients with sepsis, intermediate (36%) for patients with pneumonia and aspiration pneumonitis, and lowest (11%) for patients with trauma, there was no evidence of differential efficacy of low tidal volume ventilation in different groups with ALI or ARDS. The investigators concluded that the recommendations for low tidal volume ventilation should be applied to all patients with ALI or ARDS regardless of the inciting cause.

Important advances in the ventilatory management of patients with ALI or ARDS have led to improvements in the care of the ICU patient. With the impressive 9% reduction in mortality as demonstrated by the ARDSnet trial, low tidal volume mechanical ventilation should be considered as the standard of care for patients with ALI or ARDS unless a more efficacious strategy is demonstrated. Figure 74-2A and Figure 74-2B shows the protocol used at the University of California, San Francisco (UCSF), for mechanical ventilation of patients with ALI or ARDS.