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Myths in Emergency Medicine

Tidal Volume, False Dichotomies, and Straw Man Comparators

Spiegel, Rory, MD

doi: 10.1097/01.EEM.0000554288.10356.43
Myths in Emergency Medicine

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Lung-protective ventilation is a simple truth when managing critical care patients on mechanical ventilation. The knowledge of exactly how and when to perform such ventilatory strategies, however, is incomplete. The recent PReVENT trial adds more uncertainty to the true efficacy of low tidal volume ventilation in patients without acute respiratory distress syndrome. (JAMA 2018;320[18]:1872; http://bit.ly/2DsabZ3.)

The authors conducted a randomized controlled trial in six ICUs in the Netherlands, enrolling patients admitted to the ICU on mechanical ventilation who were not expected to be extubated within 24 hours and who did not have acute respiratory distress syndrome (ARDS), per the Berlin definition. Patients were randomized to a low (6 mL/kg) or an intermediate tidal volume strategy (10 mL/kg). The authors were permitted to utilize a volume assist control or pressure support mode of ventilation to achieve their respiratory goals.

Approximately 25 percent of 961 patients enrolled over three years were admitted post-cardiac arrest, 16 percent for pneumonia. Tidal volumes and airway pressures during the initial three days of ventilation differed significantly between the groups. No difference was seen in primary endpoint, the mean number of ventilator-free days (15.2 v. 15.5 days), nor in ICU or hospital length of stay, ICU mortality, need for a tracheostomy, or development of ARDS, pneumonia, pneumothorax, or atelectasis. The number of patients who experienced delirium in the low tidal volume group increased 6.8 percent, though this was not statistically significant (p=0.06) and should be viewed with 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 that limit this study's 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 that is limited.

The concept of low tidal volume ventilation was born from the understanding that patients with ARDS suffer from acute derecruitment of a substantial portion of their lung volume. ARDS lungs are not stiff but small. A low tidal volume strategy was originally intended to deliver a volume that was appropriate for the size of the lung being ventilated. This physiological concept was proven by the ARMA trial, which found an 8.8 percent decrease in mortality in patients randomized to low tidal volume ventilation compared with those randomized to standard ventilation strategy. (N Engl J Med 2000;342[18]:1301; http://bit.ly/2Dssduf.) Further support for a low tidal volume approach came from a meta-analysis by Serpa Neto, et al., which reported a decrease in mortality in patients without ARDS who were ventilated using a low tidal volume strategy. (JAMA 2012;308[16]:1651; http://bit.ly/2Dq1C0Q.) The IMPROVE trial, which randomized patients undergoing high-risk abdominal surgery to a low tidal volume ventilatory strategy or standard nonprotective approach, offered more evidence of benefit. (N Engl J Med 2013;369[5]:428; http://bit.ly/2DsvQAg.) The authors reported a statistically significant decrease in the rate of extrapulmonary or pulmonary complications (10.5% v. 27.5%) in patients randomized to the lung-protective approach.

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A Detrimental Strategy

We rarely consider the control group when evaluating data supporting the use of low tidal volume ventilation. The authors of the ARMA trial randomized patients to low tidal volume ventilation at 6 mL/kg and traditional ventilation at 12 mL/kg. (N Engl J Med 2000;342[18]:1301; http://bit.ly/2Dssduf.) I think we would all agree there is nothing traditional about 12 mL/kg. In fact, the traditional strategy at the time was to vary tidal volumes based on the patient's lung compliance. The median prescribed tidal volume prior to randomization was 10 mL/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 ARMA. (N Engl J Med 1998;338[6]:355; http://bit.ly/2DsdPCs; Am J Respir Crit Care Med 1998;158[6]:1831; http://bit.ly/2DrPxsf; Crit Care Med 1999;27[8]:1492; N Engl J Med 1998;338[6]:347; http://bit.ly/2Dt2iTm.) Only one demonstrated benefit and, like ARMA, compared low tidal volume ventilation with a ventilatory strategy that employed 12 mL/kg. (N Engl J Med 1998;338[6]:347; http://bit.ly/2Dt2iTm.) The three trials that failed to find benefit in a low tidal volume strategy used more conservative tidal volumes in their control group (a mean tidal volume of 10 mL/kg).

The IMPROVE trial used a similar straw man comparator, a goal tidal volume of 10-12 mL/kg with no PEEP in the control group. (N Engl J Med 2013;369[5]:428; http://bit.ly/2DsvQAg.) Even the Serpa Neto, et al., meta-analysis has significant limitations: About half of patients originated from one study with a before-and-after design examining low tidal volume ventilation in those undergoing single lung ventilation for a lobectomy. (Crit Care 2009;13[2]:R41; http://bit.ly/2DrRgxJ.)

Was ARMA positive because the authors identified a true benefit in a low tidal volume strategy or because harm was caused by a deleterious control strategy? ARMA demonstrated that a 6 mL/kg ventilatory strategy was superior to an approach that strives for tidal volumes of 12 mL/kg. What is unclear from ARMA is whether an empiric 6 mL/kg strategy is superior to simply titrating the tidal volume to the size of the lung. After all, existing data suggest that 6 mL/kg is a poor predictor of actual lung volume of any patient.

A subgroup analysis examined patients in the ARMA cohort and subdivided them based on individual patients' lung compliance at the time of randomization. (Crit Care Med 2005;33[5]:1141.) In patients with low pulmonary compliance, the low tidal volume arm demonstrated a significant improvement in mortality compared with the traditional volume group. Conversely, in patients with high pre-randomization compliance, the low tidal volume group demonstrated 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 mL/kg, and the overall mortality was 31.7 percent, almost identical to the 31 percent reported in the low tidal volume group. (Crit Care Med 2005;33[5]:1141.)

The PReVENT trial did not demonstrate the superiority of one designated tidal volume over another, but highlighted that in a group 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 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 squeezed into ventilatory boxes based on 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, we should shift our concept of mechanical ventilation away from one of compulsory prescriptions to a tool that adjusts to fit the patient and his current critical care needs.

Dr. Spiegelis a clinical instructor in emergency medicine and a critical care fellow in the division of pulmonary and critical care medicine at the University of Maryland Medical Center. Visit his blog athttp://emnerd.com, follow him on Twitter @emnerd_, and read his past articles athttp://bit.ly/EMN-MythsinEM.

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