Tidal Volume Strategies for those without ARDS

Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A, et al. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2018;320(18):1872–1880. doi:10.1001/jama.2018.14280


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 Invasive ventilation is one of the most frequently applied interventions utilized for critically ill patients.  However, as with all medical interventions, there are potential risks and harms which must be balanced with perceived benefit.  As our understanding of physiology grows, we have found more and more potential harms associated with invasive mechanical ventilation.  

Invasive mechanical ventilation is typically applied using a ventilator and either endotracheal intubation or tracheostomy. Potential harms include ventilator-associated pneumonia, tracheal stenosis, barotrauma, and need for sedation and paralysis leading to prolonged ICU stays, deconditioning, and delirium.

In 2000, the landmark ARDSNet trial was published. This looked at patients with Acute Lung Injury(ALI) and Acute Respiratory Distress Syndrome (ARDS), and compared traditional tidal volumes versus lower tidal volumes.  Simply put, ALI/ARDS are lung conditions characterized by difficulties in oxygenation and ventilation due to widespread pulmonary inflammation.  The ARDSNet trial found that these patients had much better outcomes if their tidal volumes were restricted to 6 ml/kg (Predicted Body Weight), rather than the more traditional 12 ml/kg.  This new lower tidal volume goal has generally become the standard of care for ventilated patients.

However, some feel that this lower tidal volume strategy might now be over-applied.  Not all patients who are invasively ventilated are suffering from ARDS.  In these patients, higher tidal volume strategies might be possible.  Lower tidal volume strategies also have potential harms, including increased need for sedation, patient-ventilator asynchrony, possible self-inflicted injury doe to compensatory inspiratory efforts, and respiratory acidosis due to decreased minute ventilation. 

This paper is the result of the Protective Ventilation in Patients Without ARDS (PReVENT) trial.  The study was conducted to test whether a ventilation strategy using low tidal volumes is superior to a ventilation strategy using intermediate tidal volumes.  It was a randomized clinical trial conducted in the ICUs of 6 different hospitals in the Netherlands.  Patients were enrolled if they received invasive ventilation shortly before or after admission to the ICU and who were not expected to be extubated within 24 hours of randomization.  Patients were to be randomized within 1 hour of ventilation in the ICU.  Exclusion criteria included the presence of ARDS, pediatric patients, pregnancy, increased intracranial pressure, history of pulmonary disease, and pulmonary embolism.

Patients assigned to the low tidal volume group started at a tidal volume of 6 ml/kg of PBW, and received either volume-controlled or pressure support ventilation.  If possible, tidal volume was then decreased to a minimum of 4 ml/kg.  The intermediate group started at a tidal volume of 10 ml/kg, but could be decreased for high plateau pressures if necessary.  The assigned ventilator strategies were continued for a maximum of 28 days.  They also had strict ventilator weaning algorithms. 

A total of 961 patients were enrolled – 477 in the low tidal volume group and 484 in the intermediate tidal volume strategy.  The baseline characteristics were well-balanced between the two groups.  The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included ICU and hospital length of stay, mortality, and the occurrence of pulmonary complications such as ARDS, Ventilator-Associated Pneumonia, severe atelectasis, and pneumothorax. 


As mentioned above, the primary outcome was the number of ventilator-free days and alive at day 28.  At the conclusion of the trial, patients in both groups had a median of 21 ventilator-free days.  Median length of ICU and hospital stay, ICU and hospital mortality rates, and mortality at 28 and 90 days were not different between groups.  Other secondary outcomes such as occurrence of ARDS, pneumonia, severe atelectasis, and pneumothorax also did not significantly differ.  Finally, there was no difference between groups in regard to their requirement for sedation, analgesia, or paralytics.

Essentially, there was no significant difference in any of the examined outcomes between the low tidal volume and intermediate tidal volume groups. 


This study is limited for several reasons.  Blinding was not performed/not possible due to the nature of the intervention.  A substantial number of patients were eligible but missed for randomization – as the short time to randomization was both a strength and potential liability of this trial.  However, this may have led to some selection bias for the patients who, for various reasons, were able to be so quickly randomized and enrolled.  It’s also somewhat implicitly assumed that tidal volume is the main factor contributing to ventilator associated lung injury, but as we all know there are many more factors at play (such as I:E ratio, PEEP, FiO2, driving pressure, etc) that may play large roles as well.


I think this article is particularly relevant to those in the Critical Care Transport field.  We commonly transport ventilated patients.  However, I do think there has been an over-generalization of the low tidal volume strategy advocated due to ARDSNet, and I was excited to see this paper come out and at least show the non-inferiority of an intermediate volume strategy.  The initial ARDSNet trial essentially compared a high tidal volume (12 ml/kg) ventilatory strategy versus a low tidal volume strategy, and this trial evaluated the viability of a median strategy.

Although some of our ventilated patients do in fact have ARDS, it is at least as common that they are intubated for extrapulmonary causes. For instance:  trauma, intracranial bleeding with altered mental status, angioedema, upper GI bleeding, sepsis, etc.  Even many of our patients with respiratory issues are recently intubated, and so may not have developed criteria for true ARDS at the time of transfer.

This paper justifies utilizing a higher tidal volume strategy for our patients without primary ARDS/pulmonary disease.  This can be very useful.  Patient comfort and patient-ventilator synchrony are extremely important.  This is especially true for our current emphasis on providing ideal sedation and analgesia, obviating the need for paralysis unless absolutely necessary.  With a higher tidal volume, patients can be kept on a lower respiratory rate to maintain the same minute ventilation, which is much more comfortable.  It will also lessen the likelihood of breath-stacking or AutoPEEP.  In addition, the minute ventilation can be more easily increased to compensate for acidemia, if necessary.

 Overall, this paper is important evidence to prove the viability of intermediate tidal volume ventilation, particularly in patients who are not suffering from ARDS.   

As Dr. Chris Nickson said – “the ultimate armor against fear and failure is hard-won competence.”


Andrew Cathers, MD - Dr. Cathers is an Emergency Medicine Physician as well as Flight Physician, and Assistant Medical Director of University of Wisconsin Med Flight with a focus on Education and Training in their Program. He is kind enough to share recaps of recently published HEMS literature which should be posted quarterly here on TamingtheSRU

Peer Review/Editing/Posting provided by Jeffery Hill, MD MEd