Lung-protective ventilation is often considered a simple truth when managing critical care patients on mechanical ventilation. Despite this sense of certainty, the knowledge of exactly how and when to perform such ventilatory strategies is incomplete. The recently published PReVENT adds yet more uncertainty to the true efficacy of low tidal volume ventilation in patients without ARDS1.
The authors conducted an RCT in 6 ICUs throughout the Netherlands, enrolling patients admitted to the ICU on mechanical ventilation, who were not expected to be extubated within 24-hours of admission, and who did not have ARDS (as per the Berlin definition) on admission. Patients were randomized to either a low (6 cc/kg) or an intermediate-tidal volume strategy (10 cc/kg). The authors were permitted to utilize either a volume assist control or pressure support mode of ventilation to achieve their respiratory goals.
Over a three year period the authors enrolled 961 patients, approximately 25% were admitted post cardiac arrest and an additional 16% admitted for pneumonia. During the initial three days of ventilation, tidal volumes and airway pressures differed significantly between the two groups. The authors found no difference in their primary endpoint, the mean number of ventilator-free days (15.2 vs 15.5). Nor did they observe a difference in the ICU or hospital length of stay, ICU mortality, the development of ARDS, development of pneumonia, pneumothorax, atelectasis, or need for a tracheostomy. There was a 6.8% increase in the number of patients who experienced delirium in the low-tidal volume group, though this did not reach statistical significance (p of 0.06), and thus should be viewed with an appropriate amount of skepticism.
Many have questioned these results, citing significant heterogeneity between the groups, lack of blinding, and inadequate separation in achieved tidal volumes between groups as potential sources of bias limiting this study’s internal and external validity. These confounders may explain why these results diverge from our common beliefs regarding low-tidal volume ventilation. On the other hand, PReVENT may represent the true effects of low-tidal volume ventilation in patients without ARDS and it is our interpretation of the literature which is limited.
The concept of low-tidal volume ventilation was born from the understanding that patients with ARDS suffered from an acute derecruitment of a substantial portion of their lung volume. ARDS lungs are not stiff lungs, but rather small lungs. A low tidal volume strategy was originally intended to deliver a volume that was appropriate for the size of the lung participating in ventilation. Proof of this physiological concept was demonstrated by the results of the ARMA trial which found a 8.8% decrease in mortality in the patients who were randomized to the low-tidal volume ventilation compared to those randomized to a standard ventilation strategy2. Further support for a low-tidal volume approach was bolstered by a meta-analysis published in JAMA, by Serpa et al, which reported a decrease in mortality in patients without ARDS who were ventilated using a low-tidal volume strategy3. And finally, in 2013 the NEJM published the results of the IMPROVE trial, by Futlier et al, which randomized patients undergoing high risk abdominal surgery to low-tidal volume ventilatory strategy or standard, non-protective approach4. The authors reported a statistically significant decrease in the rate of extrapulmonary or pulmonary complications (10.5% vs 27.5%) in the patients who were randomized to receive the lung protective approach.
We rarely consider the control group when evaluating the data supporting the use of low-tidal volume ventilation. In the ARMA trial, the authors randomized patients to low-tidal volume ventilation at 6 cc/kg vs a traditional ventilation which was 12 cc/kg2. I think we would all agree there is nothing traditional about 12 cc/kg. In fact, the traditional ventilator strategy at the time ARMA was enrolling was to vary tidal volumes based on the individual lung compliance of the patient. The median prescribed tidal volume prior to randomization was 10cc/kg, leading to an increase in tidal volumes in the majority of patients randomized to the traditional ventilation group. Clearly the traditional ventilation group, was exposed to extraordinarily high tidal volumes.
There were four additional trials examining the efficacy of low-tidal volume ventilation prior to the publication of ARMA5,6,7,8. Only one of these trials demonstrated a benefit, and like ARMA it compared low-tidal volume ventilation to a ventilatory strategy that employed 12cc/kg8. The three trials which failed to find a benefit in a low-tidal volume strategy all used more conservative tidal volumes in their control group (mean tidal volume of 10 cc/kg)5,6,7. The IMPROVE trial used a very similar straw man comparator, a goal tidal volume of 10-12 cc/kg with no PEEP in the control group. Even the Serpa et al meta-analysis has significant limitations. Approximately half the patients included in this meta-analysis originated from a single study9 with a before and after design examining the use of low-tidal volume ventilation in patients undergoing single lung ventilation for a lobectomy.
Was ARMA positive because the authors identified a true benefit in a low-tidal volume strategy, or was it positive because of the harm caused by a deleterious control strategy? ARMA demonstrated that a 6 cc/kg ventilatory strategy was superior to an approach which strives for tidal volumes of 12 cc/kg. What is unclear from the ARMA results is whether an empiric 6 cc/kg strategy is superior to simply titrating the tidal volume to the size of the lung participating in ventilation. After all, existing data suggest that 6cc/kg is a poor predictor of actual lung volume on any given patient. In a subgroup analysis of the ARMA data performed by Deans et al published in Critical Care Medicine in 200510, the authors examined the patients in the ARMA cohort and subdivided them based off the individual patient’s lung compliance at the time of randomization. In patients with low pulmonary compliance, the low-tidal volume arm demonstrated a significant improvement in mortality when compared to the traditional tidal volume group. Conversely, in the patients with high pre-randomization compliance, the low tidal-volume group demonstrated an increased mortality. In the group of patients who met inclusion criteria, but were not enrolled in the ARMA cohort because of technical reasons, the mean tidal volume was 9 cc/kg. The overall mortality was 31.7%, almost identical to the 31% reported in the low-tidal volume group10.
The results of the PReVENT Trial do not demonstrate the superiority of one designated tidal volume over another, but do highlight that in a group of patients without ARDS, rich with pulmonary redundancy, a larger empirically selected tidal volume is unlikely to lead to injury. The fact that larger tidal volumes are unlikely to be injurious in this subset of patients does not mean they are optimal. Rather, tidal volumes should be individually titrated to the size of the lung participating in ventilation. In lieu of such an individualized approach, patients are often forcefully squeezed into neat ventilatory boxes based off false dichotomies, limited data and straw man comparators.
In the modern ICU where a patient’s participation can no longer be chemically coerced through heavy-handed sedation packages, we should shift our concept of mechanical ventilation away from one of compulsory prescriptions, to a tool which adjusts to fit the patient and their current critical care needs.
University of Maryland
Resuscitation Fellowship Graduate