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Prevention and Management of Ventilator-Induced Lung Injury
The recognition that lifesaving mechanical ventilation can also be harmful, even lethal, has led to a sea change in the use of mechanical ventilation in critically ill patients -- at least in theory. For people with acute respiratory distress syndrome (ARDS), the primary goal of care in the previous era was to normalize gas exchange. Mounting empirical experience shows that in fact, patients with ARDS fare much better when the minimization of iatrogenic lung injury is the primary goal of mechanical ventilation. Effecting this in practice means treatment teams must often accept gas exchange values and severe acidemia that appear barely compatible with life, to be endangering other organs' function and recovery from injury, or in competition with other legitimate treatment goals.
Numerous strategies to reduce lung overdistension and prevent ventilator-induced lung injury have been tested in randomized trials:
Low Tidal Volume Ventilation
The seminal ARDSNet trial (NEJM 2000) found that a tidal volume strategy of 6 mL/kg ideal body weight resulted in a 9% absolute reduction in all-cause mortality (31% vs. 40%), as compared to a strategy using 12 mL/kg. At least 14 other randomized trials have tested low tidal volume ventilation against larger tidal volumes (~6 mL/kg vs ~10 mL/kg) and concluded that low tidal volumes are better for patients. Notably though, most of these trials did not test meaningful clinical outcomes, instead relying on soft endpoints (e.g., cytokines in bronchoalveolar lavage fluid).
Low tidal volume mechanical ventilation strategies may also prevent the development of lung injury and respiratory complications in patients without ARDS. A randomized trial showed the use of low-tidal volume ventilation improved respiratory outcomes in patients without ARDS undergoing elective abdominal surgery. A large meta-analysis including randomized trials and a larger observational pool of patients showed a strong association between low tidal volumes (~6.5 mL/kg) and reduced mortality, ARDS, and pneumonia, compared to higher tidal volumes (~10 mL/kg) among patients being mechanically ventilated but without initial ARDS.
Despite its benefits, low tidal volume ventilation has been adopted haphazardly by physicians. Even at top academic medical centers -- and at the ARDSNet centers themselves -- close adherence with low tidal volume ventilation even for patients with clear indications (ARDS) may be low. Low tidal volumes are uncomfortable for patients, often resulting in ventilator dyssynchrony ("fighting the vent") and conflict with other ICU goals like minimizing sedation. Physicians and respiratory therapists may feel uncomfortable accepting the poor gas exchange parameters, and increase tidal volumes unnecessarily. Or height may simply not be measured -- a particular problem when treating women and shorter men with ARDS, who often receive excessive tidal volumes.
High PEEP and Recruitment Maneuvers
High positive end-expiratory airway pressure (PEEP) may be necessary to stent open diseased alveoli in ARDS, cardiogenic pulmonary edema or other forms of respiratory failure, and thereby prevent atelectrauma and ventilator-induced lung injury. On the other hand, higher PEEP also carries theoretical risks for causing VILI through overdistension, or organ perfusion by impairing venous return to the heart. A higher PEEP strategy may be helpful among patients with ARDS (PaO2:FiO2 ratio < 200 mm Hg): a meta-analysis concluded higher PEEP (about 15 vs 9 cm H2O on day 1) reduced mortality by an absolute 5% in these patients. There was a 1.6% absolute increase in pneumothorax (almost always nonfatal) in the higher-PEEP groups.
Recruitment maneuvers (e.g., setting PEEP to 40 cm H2O for 40 seconds) inflate ("recruit") unaerated portions of lung, which may beneficially remain open and participatory in gas exchange thereafter. Recruitment maneuvers may improve oxygenation, but have not been evaluated thoroughly; owing to their theoretical risks for pneumothorax or reduced venous return, recruitment maneuvers' appropriate role (if any) in ventilator management is unknown.
Use of Esophageal Pressure Monitors
Talmor et al showed that using esophageal pressure monitors to target ventilator settings to transpulmonary pressure (see part 1 of this review) improved oxygenation and respiratory system compliance, compared to usual care using plateau pressure (airway occlusion pressure), in patients with ARDS. Additional randomized trials testing the use of esophageal manometry for ARDS are underway.
High Frequency Oscillatory Ventilation
In high frequency oscillatory ventilation (HFOV) or "jet ventilation," the ventilator pushes small volumes of air as many as 15 times per second into the airway, creating complex airflow phenomena in the respiratory system. Airway pressure is maintained, assuring oxygenation; carbon dioxide is removed largely through turbulent gas mixing, rather than the normal bulk flow of conventional ventilation.
By reducing atelectrauma to near zero, HFOV is in theory a highly lung-protective ventilator strategy, and gained consideration as a first-line therapy for ARDS after a meta-analysis of 8 randomized trials (n=417) suggested HFOV reduces mortality in ARDS (risk ratio 0.77). However, two subsequent large randomized trials testing HFOV for ARDS (n=1,340) showed no benefit and possible harm, as compared to conventional low tidal volume mechanical ventilation. High frequency oscillatory ventilation is today considered a salvage therapy for ARDS, not first-line, by most experts.
Face-down (prone) positioning improves oxygenation in most patients with ARDS, possibly by naturally improving lung aeration and perfusion, reducing atelectasis, and reducing pressure from the heart. A meta-analysis of 7 randomized trials (n=1,724) showed an absolute 10% improvement in mortality among prone-positioned patients with the most severe ARDS (P:F ratio < 100 mm Hg). A randomized trial of 456 patients showed a 50% reduction in mortality (33% vs 16%) in those treated with prone positioning for ARDS at highly experienced centers. Perhaps because pressure ulcers, endotracheal tube obstruction, and chest tube dislodgment were significantly more common in prone positioned patients in earlier trials, most centers have not yet adopted prone positioning as standard care for ARDS.
Extracorporeal Membrane Oxygenation (ECMO)
The ultimate lung-protective strategy might be not use the lungs for gas exchange, as in extracorporeal membrane oxygenation (ECMO). ECMO may be delivered on a full or only partial basis, supporting rather than replacing mechanical ventilation. Past randomized trials, the largest being CESAR, have not established any role for ECMO in ARDS. However, improvements in technology and growing familiarity by trained staff are resulting in institutional experience with ECMO for ARDS at major centers, who are starting to publish promising outcomes data. Numerous clinical trials testing ECMO in the management of ARDS are planned or in process.
With appreciation to:
Arthur Slutsky and V. Marco Ranieri. Ventilator-Induced Lung Injury. N Engl J Med 2013; 369:2126-36.