Low tidal volume ventilation (LTVV) has come to the forefront of ventilator management in critical care over the past two decades. Originally conceived as a lung-protective strategy in intubated patients with acute lung injury and acute respiratory distress syndrome (ARDS), LTVV is now used to manage many mechanical ventilation patients without ARDS. The logic seems sound; if this strategy works for ARDS, it may prevent harm to patients without lung injury. Unfortunately, LTVV also carries some negative consequences. Patients tend to be less comfortable and there is a higher rate of patient-ventilator asynchrony. Multiple studies have shown significant survival benefit and decreased barotrauma using LTVV (Serpa Neto et al. JAMA. 2012;308:1651-1659). Many of these studies compared LTVV strategies with high tidal volume ventilation strategies (> 10 mL/kg ideal body weight [IBW]).
The PReVENT Trial (Simonis et al. JAMA. 2018;320;1872-1880) was a randomized clinical trial performed in 6 ICUs in the Netherlands, with 961 enrolled patients. Patients were randomized to either low or intermediate tidal volume groups within one hour of initiation of invasive mechanical ventilation. The low tidal volume group started at 6 mL/kg IBW, which was then decreased by 1 mL/kg/hr to a minimum tidal volume of 4 mL/kg. This was achieved with either volume- or pressure-controlled ventilatory modes. The intermediate tidal volume group initially received 10 mL/kg, titrated to maintain plateau pressure < 25 cm H2O. The primary outcome was the number of days the patient was alive and off the ventilator at day 28. Secondary outcomes included length of stay in the ICU and hospital, mortality at 28 and 90 days, and pulmonary complications. The randomized groups had similar demographics and characteristics at baseline. Both groups were found to have the same number of alive ventilator-free days at 28 days and no significant differences in secondary outcomes or safety.
This study had many strong features. It was a well-designed, large, multicenter trial with a cohesive and implementable protocol. It also was the first large study that looked at LTVV for patients without ARDS. Most importantly, it used a comparison tidal volume of 10 mL/kg, which is more consistent with current prevailing everyday practice than prior studies that used 12 mL/kg. There were some limitations in terms of being able to translate this outcome immediately to clinical practice. First, because of the protocol that required patients to be randomized in under one hour, 704 possible enrollees were missed. The enrolled patients were quite heterogeneous, and while the study was appropriately powered for the primary outcome, there may be differences in efficacy with different diseases. And perhaps most importantly, as our understanding of lung physiology and ventilator strategies evolves, the focus on tidal volume being the “lung protection variable” may be misplaced, with other promising data points such as mechanical power or driving pressure being better indicators of protection or harm.
This study is helpful as it suggests that low tidal volume (4-6 mL/kg IBW) and reasonable tidal volume (≤10 mL/kg IBW with plateau pressure < 25 cm H2O) are equivalent in patients without ARDS. Therefore the clinician has more leeway to adjust the ventilator to keep the patient comfortable without causing harm. For a patient without ARDS who is not tolerating low tidal volumes well and is requiring large doses of sedation or who is unable to manage respiratory acidosis, it is likely safe to increase the tidal volume for comfort and tolerance without adversely affecting the patient’s overall outcomes, provided that the tidal volume remains ≤ 10 mL/kg IBW with plateau pressure < 25 cm H2O.
Coauthors of this installment of Concise Critical Appraisal:
Neil Dasgupta, MD, is an assistant professor and clinical resuscitation fellow in the Department of Emergency Medicine at Stony Brook Medicine.
Brian J. Wright, MD, MPH, is a clinical associate professor and program director of the Advanced Resuscitation Training Program in the Department of Emergency Medicine at Stony Brook Medicine. Dr. Wright is an editor of Concise Critical Appraisal.