Noninvasive ventilation halves risk of hypoxia during emergency intubation: Results of the PREOXI trial

In current clinical care, most critically ill adults undergoing emergency endotracheal intubation receive preoxygenation via oxygen mask. Providing supplemental oxygen to patients before the intubation procedure begins increases the oxygen content of the patient's lungs and reduces the risk of hypoxia (low oxygen levels in the blood). However, hypoxia occurs in 10% to 20% of endotracheal intubations in the emergency department or intensive care unit and can lead to cardiac arrest and death.

The University of Colorado, in collaboration with Vanderbilt University, led a trial comparing the two most common ways of giving patients supplemental oxygen before intubation: supplemental oxygen via noninvasive ventilation and supplemental oxygen via oxygen mask. The trial, called Pragmatic Trial of Supplemental Oxygen Before Intubation (PREOXI), was conducted by the Pragmatic Critical Care Research Group (PCCRG) in 24 emergency departments and intensive care units across the U.S. Of the 1,301 patients in the trial, 120 were enrolled at UCHealth University of Colorado Hospital.

Studies have shown that noninvasive ventilation – which involves delivering air at higher pressure to the airways using a tight-fitting breathing mask connected to a bilevel positive airway pressure (BiPAP) machine – cuts the risk of hypoxia in half and significantly reduces the risk of cardiac arrest compared with oxygen mask ventilation.

Adit Ghinde, MD, MPH, co-senior principal investigator of the study and professor of emergency medicine at the University of Colorado School of Medicine, is affiliated with the University of Colorado's Center for Combat Medicine and Battlefield (COMBAT) Research, which obtained funding for the research from the U.S. Department of Defense.

We believe the results of this study will change the way patients are cared for across the country and around the world, leading to better outcomes for life-saving intubation procedures. [study] “These facilities are extremely motivated to transform and improve clinical care for the U.S. Military, the sponsor of this study, and for the general public.”

Adit Ghinde, MD, MPH, co-principal investigator on the study and professor of emergency medicine at the University of Colorado School of Medicine

This study is published today: New England Journal of Medicine.

Important practice-changing results

During the trial, critically ill adults undergoing endotracheal intubation were randomly assigned to one of two groups: preoxygenation with noninvasive ventilation or preoxygenation with an oxygen mask.

Investigators studied whether preoxygenation with noninvasive ventilation prevents hypoxia during intubation.

Of 1,301 patients rapidly enrolled over a 17-month period, hypoxemia occurred in 57 of 624 (9.1%) in the noninvasive ventilation group and 118 of 637 (18.5%) in the oxygen mask group. Furthermore, by preventing hypoxemia during tracheal intubation, preoxygenation with noninvasive ventilation also prevented cardiac arrest in 1 patient (0.2%) in the noninvasive ventilation group and 7 patients (1.1%) in the oxygen mask group.

“By using BiPAP, a non-invasive ventilation technique, we can cut the amount of this complication, low oxygen levels, in half,” Ginde says. “The magnitude of this effect is unusual to see such a large improvement in outcomes in a clinical trial, let alone a critical care trial. An important secondary result is that the rate of cardiac arrest was also lower in the non-invasive ventilation group.”

Prior to this trial, international guidelines stated that pre-oxygenation, either by non-invasive ventilation or an oxygen mask, was acceptable, providing guidance that the results of this trial would likely have been different.

Colorado leads breakthrough clinical significance

Ginde is eager to begin implementing the changes and recommendations locally and around the world. His teams at the University of Colorado and UCHealth are partnering with the University of Colorado Center for Combat Studies and the U.S. Army to work on immediate changes to military clinical practice guidelines. Nine of the study authors are affiliated with the University of Colorado's departments of emergency medicine, internal medicine, and anesthesiology, and Ginde hopes for a smooth transition to the new practice standards.

“We have already begun clinical implementation at our institution, the University of Colorado UCHealth Hospital, and all other PCCRG institutions participating in this trial,” Ginde said, “and have begun working with military operational and combatant commands and integrated trauma systems to change policies and training guidelines.”

Ginde emphasized the importance of CU's team effort and leadership in the research, including its connections with the military and its leadership role in obtaining funding.

“This has been a huge team effort. The PCCRG is a highly effective group of facilities leading critical care clinical trials across the country,” he said. “This study would not have been possible without their work facilitating funding from the Defense Health Agency through our partners at the CU Combat Research Center and the U.S. Air Force 59th Medical Wing Science and Technology Directorate.”