May 122012
Mechanical Ventilation in ARDS: 2014 Review
(More PulmCCM Topic Updates)

People with acute respiratory distress syndrome (ARDS) are by definition severely hypoxemic, and nearly all require invasive mechanical ventilation. Yet mechanical ventilation itself can further injure damaged lungs (so-called ventilator-induced lung injury); minimizing any additional damage while maintaining adequate gas exchange ("compatible with life") is the central goal of mechanical ventilation in ARDS and acute lung injury, its less-severe form.

Benefits of Low Tidal Volume Ventilation in ARDS

Low tidal volume ventilation (LTVV) reduces the damaging, excessive stretch of lung tissue and alveoli (so-called volutrauma), and is the standard of care for people with ARDS requiring mechanical ventilation. Although ARMA, the largest clinical trial supporting this paradigm, was criticized both for its design and for ethical concerns, its results (published in 2000 by ARDSNet), followed by two flawed but concordant meta-analyses [1, 2] including ten randomized trials total, have convinced most intensivist physicians that using low tidal volumes improves survival for people with ARDS. Taken together, the trials suggest that a strategy of low tidal volume ventilation (6-8 mL/kg ideal body weight) reduces absolute mortality by about 7-9%, as compared to using >= 10 mL/kg tidal volumes (~42% mortality in control groups vs. ~34% in the LTVV groups). This translates to a "number needed to treat" of between 11-15 people with ARDS to prevent one death by using LTVV.

How to Use Low Tidal Volume Ventilation in ARDS

The protocol from the ARMA trial can serve as a guide to performing low tidal volume ventilation for mechanically ventilated patients with ARDS:

  • Start in any ventilator mode with initial tidal volumes of 8 mL/kg predicted body weight in kg, calculated by: [2.3 *(height in inches - 60) + 45.5 for women or + 50 for men].
  • Set the respiratory rate up to 35 breaths/min to deliver the expected minute ventilation requirement (generally, 7-9 L /min)
  • Set positive end-expiratory pressure (PEEP) to at least 5 cm H2O (but much higher is probably better), and FiO2 to maintain an arterial oxygen saturation (SaO2) of 88-95% (paO2 55-80 mm Hg). Titrate FiO2 to below 70% when feasible (though ARDSNet does not specify this).
  • Over a period of less than 4 hours, reduce tidal volumes to 7 mL/kg, and then to 6 mL/kg.

Ventilator adjustments are then made with the primary goal of keeping plateau pressure (measured during an inspiratory hold of 0.5 sec) less than 30 cm H2O, and preferably as low as possible, while keeping blood gas parameters "compatible with life." High plateau pressures vastly elevate the risk for harmful alveolar distension (a.k.a. ventilator-associated lung injury, volutrauma). If plateau pressures remain elevated after following the above protocol, further strategies should be tried:

  • Further reduce tidal volume, to as low as 4 mL/kg by 1 mL/kg stepwise increments.
  • Sedate the patient (heavily, if necessary) to minimize ventilator-patient dyssynchrony.
  • Consider other mechanisms for the increased plateau pressure besides the stiff, noncompliant lungs of ARDS.

As a last resort, neuromuscular blockade can be employed to reduce plateau pressure by eliminating patient effort, muscle tone and dyssynchrony. However, this approach has unquantified risks of long-term neuromuscular weakness and disability.

Permissive Hypercapnia in ARDS

This single-minded focus on reducing plateau pressures derives from the likely survival benefit from low tidal volume ventilation and low plateau pressures observed in clinical trials (or if you prefer, the harmful effects seen from using "normal" or physiologic tidal volumes with resulting high plateau pressures in those trials).

Achieving these low plateau pressures usually requires tidal volumes low enough to result in hypoventilation, with resulting elevations in pCO2 and respiratory acidemia that can be severe and to the treating physician, anxiety-provoking. This approach, "permissive hypercapnia," represents a paradigm shift from previous eras, in which achieving normal blood gas values was the main goal of mechanical ventilation.

How "permissive" can one be? Mechanically ventilated patients with ARDS appear to tolerate very low blood pH and very high pCO2s without any adverse sequelae (defying physicians' anxieties based on intuition, training and medical lore):

  • Current consensus suggests it is safe to allow pH to fall to at least 7.20.
  • The actual pCO2 is of little importance.
  • When pH falls below 7.20, many physicians choose to administer sodium bicarbonate, Carbicarb, or THAM to maintain blood pH between 7.15 - 7.20.
  • However, it is unknown whether such correction of acidemia is helpful, harmful, or neither (good evidence is lacking for any of these hypotheses).

Conditions in which permissive hypercapnia for ARDS could theoretically be harmful include cerebral edema, mass lesions or seizures; active coronary artery disease; arrhythmias; hypovolemia; GI bleeding, and possibly others. These are hypothetical harms based on pathophysiology and not outcomes data, while the harm of ventilator induced lung injury and the benefits of a protective ventilator strategy in ARDS are real and known. The potential risks of hypercapnia in such patients must be weighed against the risks of ARDS, and therapy individualized.

Limitations in Use of Plateau Pressure for ARDS

Patients with reduced chest wall compliance -- most commonly due to obesity -- may have higher plateau pressures at baseline and during ARDS than non-obese patients. It is possible that in some obese patients, titrating tidal volumes to plateau pressures < 30 cm H2O may be inadequate and result in worsened hypoventilation. There are no recommendations to treat obese patients with ALI / ARDS differently than non-obese patients with regard to mechanical ventilation. Esophageal manometry is considered superior to plateau pressures through its measurement of transpulmonary pressure, considered a more precise measure of potentially injurious pressures in the lung. Because it is invasive and the probes are prone to migration, esophageal manometry is not widely used.

Prone Positioning in ARDS

Prone positioning (face-down) improves gas exchange and has long been used as an adjunctive or salvage therapy for severe or refractory ARDS. Prone positioning is gaining credibility as a new standard of care for ARDS after a multicenter trial published in 2013, demonstrated a dramatic near-50% relative risk reduction, and a 17% absolute risk reduction for mortality. Patients were kept in prone position for 16 hours a day in that trial, which was conducted at 27 European centers highly experienced with prone positioning for ARDS. The benefits of prone positioning have not yet been replicated in a large U.S. trial, but a meta-analysis of 6 randomized trials also concluded prone positioning saves lives in ARDS when added to a lung-protective ventilatory strategy.

High vs. Low PEEP in ARDS

A strategy employing higher PEEP along with low tidal volume ventilation should be considered for patients receiving mechanical ventilation for ARDS. This suggestion is based on a 2010 meta-analysis of 3 randomized trials (n=2,229) testing higher vs. lower PEEP in patients with acute lung injury or ARDS, in which ARDS patients receiving higher PEEP had a strong trend toward improved survival.

However, patients with milder acute lung injury (paO2/FiO2 ratio > 200) receiving higher PEEP had a strong trend toward harm in that same meta-analysis. Higher PEEP can conceivably cause ventilator-induced lung injury by increasing plateau pressures, or cause pneumothorax or decreased cardiac output. These adverse effects were not noted in the largest ARDSNet trial (2004) testing high vs. low PEEP.

Predicting Survival and Outcomes After ARDS

In a 2012 retrospective analysis in JAMA including data from over 4,400 patients with ARDS enrolled in randomized trials, only the severity of hypoxemia (low PaO2/FiO2 ratio) was predictive of mortality. Commonly used clinical parameters of severity (static compliance, degree of PEEP, and extent of opacities on chest X-ray) were not predictive of outcome. A "high risk" patient profile with a 52% mortality was identified post hoc, comprised of severe ARDS (PaO2/FiO2 ratio < 100) with either a high corrected expired volume >= 13 L/min, or a low static compliance < 20 mL/cm H2O. Reviews of ARDS outcomes suggest that most people who survive ARDS recover pulmonary function, but may remain impaired for months or years in other domains, both physically and psychologically.

Alternative / Rescue Ventilator Modes & ECMO in ARDS

Some patients with severe ARDS develop severe hypoxemia or hypercarbia with acidemia despite optimal treatment with low-tidal volume mechanical ventilation. In these situations, alternative, salvage or "rescue" ventilator strategies are often employed. Their common goal is to maintain high airway pressures to maximize alveolar recruitment and oxygenation, while minimizing alveolar stretch or shear stress. The most commonly used alternative ventilatory strategies are high-frequency oscillatory ventilation (HFOV) or airway pressure release ventilation (APRV or "bilevel"). HFOV is not appropriate as a first-line treatment for ARDS. More on HFOV and APRV:

High-frequency oscillatory ventilation for adult patients with ARDS (Chan KP, Chest 2007)

Bench-to-bedside review of HFOV in adults with ARDS (Downar, Crit Care 2006)

HFOV Clinical Practice Guidelines (Prince of Wales Hospital)

What on earth is APRV? (Henzler D, Crit Care 2011)

APRV: an alternative mode of mechanical ventilation in ARDS (Modrykamien A, Cleve Clin J Med 2011)

Extracorporeal membrane oxygenation has also become a more commonly used salvage therapy for ARDS, thanks to improvements in technology making it safer and more feasible to administer. Its use is limited to specialized centers, and there are no randomized trials (since CESAR) defining its benefits, nor guidelines for its wider use.

A summary of strategies for managing refractory hypoxemia in ARDS can be found here:

Therapies for Refractory Hypoxemia in Acute Respiratory Distress Syndrome (Pipeling/Fan, JAMA 2010)

Severe Hypoxemic Respiratory Failure, Part 1, (Esan et al, Chest 2010)

There is currently a dearth of evidence to establish the role of alternative strategies for mechanical ventilation or ECMO in ARDS. Each strategy has its rationale, anecdotal efficacy, and faction of physician advocates, some of whom argue that these strategies may in fact be superior to low tidal volume ventilation, and should be considered earlier in the course of ARDS. (However, it is clear that HFOV is not appropriate as a first-line treatment for ARDS.) Testing each hypothesis would require a large, expensive randomized controlled trial; until then, low-tidal volume ventilation is the recommended and evidence-supported strategy for mechanical ventilation in ARDS.

Recent Research Findings / Controversies in ARDS

Beta-agonist infusions were found to be harmful to ARDS patients in the 2011 BALTI trials. Trophic (minimal) tube feeds appeared equivalent to full-calorie tube feeds for acute lung injury / ARDS patients in the 2011 EDEN trial. 48 hours of neuromuscular blockade early in the course of severe ARDS appeared to improve mortality in a 2010 randomized trial. These findings are mentioned for informational purposes only, without any recommendation as to their use.

More PulmCCM Topic Updates & Reviews


Read more: 

ARDSNet Protocol

ARMA Trial (N Engl J Med)


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Mechanical Ventilation in ARDS: Research Update