The landmark ARDS trial published in the New England Journal of Medicine in 2000 showed a mortality benefit for patients with ARDS that were mechanically ventilated with a low tidal volume strategy (6 ml/kg versus 12 ml/kg). There were also more ventilator free days in the low tidal volume strategy. We intubate many patients without ARDS; do these non-ARDS patients benefit from a low tidal volume strategy?

A prospective randomized trial titled Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS was published in JAMA in 2018. This was the largest randomized trial to investigate a low tidal volume strategy in patients without ARDS. The primary objective was number of ventilator free days and alive at day 28. They randomized 477 patients to low tidal volume strategy (6 ml/kg) and 484 to intermediate tidal volume strategy (10 ml/kg). The investigators discovered no difference in mortality or ventilatory free days at day 28. In order to interpret these results you have to look at the methods. Due to frequent pressure support trials in the low tidal group the mean tidal volume was 7 ml/kg. In the intermediate tidal volume group they kept the plateau pressure less than 25 cm H2O which made the mean tidal volume 9 ml/kg. Essentially, they used lung protective ventilation in the intermediate tidal volume group which biased the results towards the null hypothesis. 

Another study comparing low vs intermediate tidal volumes in patients without ARDS was published in Critical Care in 2010 titled Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized control trial. The primary outcome was to determine if a low tidal volume strategy compared to an intermediate tidal volume strategy was associated with different levels of inflammatory cytokines in lavaged and serum samples. The secondary outcome was ventilator free days after day 28 and mortality. In the low tidal volume group they found a more pronounced decrease in IL-6 and higher baseline IL-6 were found in patients that developed lung injury. They found no difference in ventilator free days or mortality although the study wasn’t powered to detect a difference and the trial was stopped early due to concerns of patients in the intermediate tidal volume group developing lung injury. If patients in the intermediate tidal volume group developed acute lung injury the tidal volumes were decreased. Although no difference in ventilator free days this trial makes a good argument that higher tidal volumes cause harm in patients without ARDS.

Both trials demonstrated that the low tidal volume group did not require more sedation, experience severe dyspnea or more patient-ventilator asynchrony.

References:

1. Determann, R., Royakkers, A., Wolthuis, E., Vlaar, A., Choi, G., Paulus, F., Hofstra, J., Graaff, M., Korevaar, J., Schultz, M.(2010). Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trialCritical Care 14(1), R1. https://dx.doi.org/10.1186/cc8230

2. Investigators, W., Simonis, F., Neto, A., Binnekade, J., Braber, A., Bruin, K., Determann, R., Goekoop, G., Heidt, J., Horn, J., Innemee, G., Jonge, E., Juffermans, N., Spronk, P., Steuten, L., Tuinman, P., Wilde, R., Vriends, M., Abreu, M., Pelosi, P., Schultz, M.(2018). Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS JAMA 320(18), 1872. https://dx.doi.org/10.1001/jama.2018.14280