The Effect of Lowering Tidal Volume on Mortality

The use of low tidal volume (4-8 ml/kg of predicted body weight) has been considered the default way to ventilate patients with acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury (VILI). Recommendations have additionally been made to use 6 ml/kg of predicted body weight as a standard setting due to the reason that ARDS can go unrecognized approximately 40% of the time.(1) It is possible that the driving pressure resulting from the tidal volume, not the tidal volume itself, determines  the risk of lung injury and mortality in patients with ARDS.(2)

A recent study published in the American Journal of Respiratory and Critical Care by Ewan Goligher and colleagues assessed the benefits of using a lower tidal volume strategy.(3) They investigated the relationship of tidal volume and driving pressure on mortality in an interesting and intuitive way using respiratory system elastance normalized to predicted body weight.  We asked Dr. Goligher the following questions to elaborate on the key information provided by this study.

What was the main goal of the study?

We set out to resolve whether the real target for lung protection should be driving pressure or tidal volume. We aimed to do this by comparing the effect of lowering tidal volume on mortality between patients with lower respiratory system elastance (in whom driving pressures would be low) and patients with higher respiratory system elastance (in whom driving pressures from the same tidal volume would be high). This comparison was made in previous randomized controlled trials varied based on respiratory system elastance. Using randomized trials allowed us to infer causation based on randomized treatment assignment. If driving pressure is the true cause of VILI then there should be a greater benefit to lowering tidal volume in patients with high elastance, and a lesser benefit in those with normal or low elastance. Additionally, we considered the possibility of harm with using lower tidal volume in patients with low elastance.

What are the possible harms of using low tidal volume?

While low tidal volume of 6 ml/kg of PBW is physiologically ‘normal’, patients with increased respiratory drive may demand higher tidal volumes. We limit tidal volume with the assumption that it will reduce VILI, but it can introduce other possible issues. Heavy sedation or possible neuromuscular blocking agents may be required to prevent the patient from demanding higher tidal volume. Lowering tidal volume can result in breath-stacking dyssynchrony (which effectively increases tidal volume!). Heavy sedation limits spontaneous breathing and patient mobility and is associated with delirium and long-term morbidity. Additionally, low tidal volume can lead to atelectasis when PEEP is not set appropriately.

Why was respiratory system elastance normalized to predicted body weight?

Elastance (and compliance) are variables that reflect ‘baby lung’ volume. Smaller ‘baby lungs’ have higher elastance (and lower compliance) due to atelectasis and consolidation and resulting lung volume loss. Because lung volume is also correlated to height, normalizing elastance to predicted body weight corrects for variations in height and the resulting value more specifically reflects variation in lung volume.  

Normalized respiratory system elastance is easy to compute and interpret. It is simply the driving pressure divided by the tidal volume (measured in ml/kg predicted body weight, as usual). A patient with a driving pressure of 12 cm H2O when tidal volume is 6 ml/kg will have a normalized elastance value 2 cm H2O/ml/kg. A patient with a driving pressure of 12 cm H2O when tidal volume is 4 ml/kg will have a normalized elastance of 3 cm H2O/ml/kg. Normalized elastance is generally less than 1 cm H2O/ml/kg in healthy subjects. This parameter gives an easy way of assessing how much lung stiffness has increased (and lung volume has decreased) compared to healthy subjects. Normalizing respiratory system elastance (ERS) is important to account for the variation in tidal volume and elastance that would be due to the height of the patient.

The authors found that the effect of lowering tidal volume from 10-12 ml/kg to 4-6 ml/kg on mortality varied widely between patients, depending on their elastance. Patients with low elastance exhibited very little mortality benefit. Patients with high elastance exhibited very large mortality benefit. Importantly, when driving pressures were less than 15 cm H2O, there was no mortality benefit from lowering tidal volume, even when tidal volume was as high as 12 ml/kg!

Based on the results of the study, the table and figures below present the probability of reducing mortality risk using a  lower tidal volume ventilation strategy.

Figures from publication(3): Posterior probabilities of various values of the treatment effect of a lower-VT ventilation strategy on mortality according to respiratory system elastance. The lower panel shows the driving pressures correlated with these probabilities of benefit or harm at varying elastance. The error bars represent the SEM.

How might a clinician use this information at the bedside?

Primarily, this study means that clinicians should aim to protect the lung primarily by targeting low lung-distending pressures. The tidal volume is only a secondary concern in that it determines how much driving pressure is generated. A driving pressure below 15 cm H2O means that harm from tidal volume is unlikely.

Sometimes this will require clinicians to lower tidal volume well below 6 ml/kg. At other times this will allow clinicians to allow tidal volume to rise well above 6 ml/kg, up to 8-10 ml/kg, as long as driving pressures remain low.

An example of this concept used clinically could be when a patient is presenting with acidosis. Clinically, you could increase minute ventilation more by increasing tidal volume and respiratory rate rather than relying on respiratory rate alone. If you assess the normalized elastance and it is ≤ 1.5, there is a low probability of benefit for using low tidal volume and increasing tidal volume (8 ml/kg) may be acceptable. Additionally, this could facilitate allowing the patient to resume spontaneous breathing without resulting in high respiratory effort. Note that it will be important to measure driving pressure and lung-distending pressure accurately during spontaneous breathing to ensure that larger tidal volumes are safe and acceptable.

1. Bellani, Giacomo, Tài Pham, and John G. Laffey. 2020. “Missed or Delayed Diagnosis of ARDS: A Common and Serious Problem.” Intensive Care Medicine 46 (6): 1180–83.

2. Amato, Marcelo B. P., Maureen O. Meade, Arthur S. Slutsky, Laurent Brochard, Eduardo L. V. Costa, David A. Schoenfeld, Thomas E. Stewart, et al. 2015. “Driving Pressure and Survival in the Acute Respiratory Distress Syndrome.” The New England Journal of Medicine 372 (8): 747–55.

3. Goligher, Ewan C., Eduardo L. V. Costa, Christopher J. Yarnell, Laurent J. Brochard, Thomas E. Stewart, George Tomlinson, Roy G. Brower, Arthur S. Slutsky, and Marcelo P. B. Amato. 2021. “Effect of Lowering Vt on Mortality in Acute Respiratory Distress Syndrome Varies with Respiratory System Elastance.” American Journal of Respiratory and Critical Care Medicine 203 (11): 1378–85.

4 thoughts on “The Effect of Lowering Tidal Volume on Mortality”

  1. Great to reassess the general use of low vt. Many times, the vt for a given pt is questionable. Yet sticking w lo vt, one is “boxed” into that strategy. This will incentivize the clinician to consider other variables when choosing a hi or lo vt strategy

  2. If I am following this correctly,

    1. Calculations must be based on an accurate mLs/kg PBW

    2. For patient’s with low elastance (high compliance) a low tidal volume strategy doesn’t decrease mortality if the driving pressure divided by the mLs/kg PBW equals a normalized elastance < 1.5.

    3. Large tidal volumes may be acceptable as long as the normalized elastance < 1.5

    4. PSV may be acceptable if the normalized elastance is 1.5 then follow lung protective guidelines (optimal PEEP, driving pressure 3 for example)

    The may be an over simplification but is this article saying: “Don’t put patient’s with good lungs on an uncomfortable low tidal volume and high rate setting”?

    I am going to track down the article and read it.

    Thank you,


    1. 1. Yes
      2. This is the idea.
      3. Probably, but within normal physiological limits.
      4. We still don’t know if controlling tidal volume during spontaneous breathing (with sedation and/or paralysis) is worse than allowing them to breath with high tidal volume. This concept of normalized elastance may by helpful.

      Your oversimplification is the concept, but has not yet been tested prospectively (but will be).

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