PREOXI: Less hypoxemia with NIV before emergency intubation

PREOXI addresses a practical emergency-airway question: does preoxygenation with noninvasive ventilation reduce hypoxemia compared with an oxygen mask? Its answer favors NIV for the patients studied. Interpreting that result requires attention to the actual treatment sequence, the patients who were excluded, and the difference between a convincing oxygenation benefit and less certain findings about aspiration, cardiac arrest, and survival.

How the study was designed

PREOXI was a pragmatic, multicenter randomized trial in critically ill adults undergoing intubation with sedation and laryngoscopy. Assignment was individual, stratified by site, and concealed until enrollment using numbered opaque envelopes. Clinicians and trial personnel knew the assigned treatment afterward. Trained observers who were not performing the intubation recorded pulse-oximetry outcomes; operators reported aspiration and cardiac arrest. The prespecified primary endpoint was saturation below 85% from induction through two minutes after intubation. The secondary endpoint was the lowest saturation during that interval. Prespecified methods (preprint).

These choices make the trial clinically recognizable while preserving an important distinction: a pragmatic design allows treatment discretion, but it still tests a defined comparison. Observer collection reduces dependence on retrospective documentation; it does not remove the possibility that knowing the assignment influenced care or event reporting. The primary oxygenation measurement and the operator's report of aspiration also have different measurement limitations.

What the two groups received

The intervention recommendations specified a tight-fitting ventilator interface, 100% oxygen, expiratory pressure of at least 5 cm H2O, inspiratory pressure of at least 10 cm H2O, and a respiratory rate of at least 10/min. Operators chose the ventilator and mode. NIV continued from preoxygenation until laryngoscopy began. The comparator was a nonrebreather or bag-mask device, without manual ventilation before induction, using the highest available oxygen flow of at least 15 L/min. Both groups aimed for at least three minutes of preoxygenation when feasible. Final protocol, intervention sections.

Bag-mask ventilation after induction and supplemental nasal oxygen were permitted in either arm. These details appear in the prespecified methods preprint; the registry compilation above contains the final protocol. The comparison therefore includes more than an interface applied to an awake patient. In particular, this was not a randomized comparison of NIV against high-flow nasal oxygen alone.

For an anesthesia reader, the treatment sequence is central to applicability. The result should not be reduced to a claim that any use of positive pressure, at any point, reproduces the intervention. Nor should the control be described as an absence of oxygenation support. Understanding what both arms could receive is necessary before comparing the trial with an existing airway practice.

The primary benefit

The trial enrolled 1,301 adults at 24 US ED/ICU sites. Hypoxemia occurred in 57/624 patients with NIV (9.1%) and 118/637 with an oxygen mask (18.5%): absolute difference −9.4 percentage points (95% CI, −13.2 to −5.6). Missing primary measurements account for the smaller outcome denominators. Original report, primary outcome.

The absolute difference makes the magnitude easier to judge than a relative reduction alone. It remains an effect on a specific physiologic endpoint during a short procedural interval. The appropriate conclusion is that NIV reduced this measured hypoxemia outcome under the trial's conditions. A survival benefit requires separate evidence, even when the physiologic result is compelling.

Safety findings: reassuring observations with important uncertainty

The original report provides these additional outcomes. Differences below are NIV minus oxygen mask, in percentage points. Original report, Table 3.

Aspiration was an exploratory safety outcome; cardiac arrest and death were exploratory outcomes. These comparisons were not adjusted for multiplicity. The US Department of Defense funded the study. Original report, statistical methods and funding.

The aspiration estimate does not show a detected increase, but its interval includes some increase as well as reduction. It cannot establish equivalent safety. Likewise, the cardiac-arrest observation is encouraging, but only eight events occurred. It should be presented as a signal requiring caution, rather than a proven arrest-prevention effect. The mortality interval does not establish improved survival.

Which patients does the evidence cover?

Eligibility required both approaches to be clinically acceptable. Immediate urgency, existing positive-pressure ventilation, apnea or hypopnea, and clinician-determined contraindications could prevent enrollment. The protocol specifically recognized active vomiting and airway or gastrointestinal bleeding among reasons NIV might be inappropriate. Eligibility and exclusion criteria.

Those boundaries are particularly important when interpreting the aspiration findings. A favorable result in selected patients cannot resolve safety for a patient excluded because aspiration risk made the intervention unacceptable. The absence of a detected harm in the randomized population should not erase the clinical selection that occurred before randomization.

Implications for CRNA practice

PREOXI supports considering NIV within a patient-specific emergency-intubation plan when the studied approach is feasible and appropriate. Its strongest finding is reduced hypoxemia, with uncertain effects on uncommon complications and survival. Applying it to routine elective induction, a different comparator, or an excluded patient requires a separate argument.

A focused departmental review can compare current practice with the trial's eligibility, equipment, timing, and permitted adjuncts. That preserves the useful clinical finding without converting one emergency-airway trial into a universal technique or a guarantee of safety.