By Vibhu Sharma, MD

Attending Physician, Division of Pulmonary and Critical Care Medicine, John H. Stroger Hospital of Cook County; Assistant Professor of Medicine, Rush University Medical Center, Chicago

Dr. Sharma reports no financial relationships relevant to this field of study.

SYNOPSIS: A post-hoc analysis of data from the MACMAN trial revealed noninvasive ventilation may be the preferred preoxygenation approach for intubation, especially in the setting of severe hypoxemia.

SOURCE: Bailly A, et al. Compared efficacy of four preoxygenation methods for intubation in the ICU: Retrospective analysis of McGrath Mac Videolaryngoscope versus Macintosh Laryngoscope (MACMAN) trial. Crit Care Med 2019;47:e340-e348.

The authors of the McGrath Mac Videolaryngoscope Versus Macintosh Laryngoscope (MACMAN) trial randomized critically ill patients undergoing endotracheal intubation to video laryngoscopy (VL) and direct laryngoscopy (DL) using a Macintosh (curved) blade. Bailly et al analyzed the four groups retrospectively for outcomes with respect to preoxygenation technique: bag valve mask (BVM) ventilation using oxygen at 15 L/minute flow (no positive-end expiratory pressure [PEEP] valve was used) for three minutes, nonrebreather (NRB) mask with oxygen at 15 L/minutes for three minutes, noninvasive ventilation (NIV) with 100% oxygen for at least three minutes, and high-flow nasal cannula (HFNC) oxygen (Optiflow) at 60 L/minute flow at 100% FiO2 for three minutes. Intubators were free to choose any one of the four methods. The association of nadir pulse oximetry (SpO2) during endotracheal intubation and two hours after intubation with the preoxygenation technique was the primary objective of the study. The secondary objectives included assessment of risk factors for SpO2 below 80%, 90%, and a composite endpoint of cardiac arrest; systolic blood pressure (SBP) < 90 mmHg; or SpO2 below 80%. During the study, standardized forms collected data, including primary diagnosis, duration of preoxygenation, duration of endotracheal intubation, baseline SpO2, and baseline PaO2/FiO2 ratio.

Models to assess factors associated with the median minimal SpO2 during intubation and two hours postintubation were identified. Logistic regression analysis models were created to identify factors associated with SpO2 < 80% and < 90% across the four preoxygenation groups (BVM, NRB mask, NIV, and HFNC), with BVM serving as the index. Multiple logistic regression analyses were performed to identify factors associated with major complications (esophageal intubation, cardiac arrhythmias, dental injuries) and serious complications (death, cardiac arrest, SpO2 < 80%, and SBP decline to < 90 mmHg).

Overall, 319 patients were included in the analysis (44 patients of the original MACMAN cohort were excluded due to multiple preoxygenation techniques used). All patients underwent rapid sequence intubation (RSI). The number of intubation attempts, duration of attempts to intubate, and proportion of intubation first attempts by a nonexpert were no different across groups. Clinical characteristics of patients in each group were similar, except for a higher proportion of patients with severe hypoxemia at baseline and those intubated for a primary respiratory diagnosis in the NIV group. While the duration of preoxygenation was longer in the NRB, NIV, and HFNC groups vs. the BVM group, it did not seem to affect the extent of drop in SpO2 around intubation. Severity of illness scores (based on Simplified Acute Physiology Score [SAPS] II) and baseline SpO2 were significant predictors of minimal SpO2 value during endotracheal intubation plus two hours after intubation.

More attempts at intubation were associated with greater declines in SpO2 levels during intubation and in the hours following intubation. Regardless of preoxygenation technique used, baseline SpO2 was predictive of how far the SpO2 would drop during and subsequent to intubation. Provision of NIV was associated with an adjusted odds ratio (aOR) of 0.10 with respect to BVM when predicting an SpO2 drop below 90% (implying a “protective” effect). HFNC was worse than BVM (aOR for hypoxemia, 5.75). Provision of a NRB mask had an aOR similar to BVM.


The authors of this retrospective analysis concluded that NIV was the most efficacious preoxygenation technique, especially for those patients with significant hypoxemia to begin with. This study comes with all the drawbacks of a post-hoc analysis, which have been well-described — namely, discovering a finding that occurs purely by chance. The authors did not detail assessment of heterogeneity of treatment differences (however, they acknowledged the groups were heterogeneous). The authors further acknowledged that the study is underpowered for some treatment effects, needing 526 patients to provide > 90% power. Most importantly, preoxygenation devices were not allocated in randomized fashion. Keeping these limitations in perspective, this study demonstrated the (likely) superiority of NIV as a preoxygenation technique and confirms my practice in preoxygenating patients in the ICU.

Bailly et al did not suggest NIV settings, and these were not standardized in the MACMAN trial and were left to the discretion of the intubating physician. The duration of preoxygenation did not seem to affect the extent of the drop in SpO2 across groups, which if confirmed in a clinical trial, would help inform the preintubation check list. Multiple attempts at intubation were associated with greater drops in SpO2, not just during intubation but also in the hours following intubation. This speaks to the importance of avoiding critical desaturation during intubation and choosing the most efficacious preoxygenation technique, especially in those with lower baseline SpO2. As noted above, NIV settings were not standardized, but typically aimed for exhaled tidal volume of 7-10 mL/kg and PEEP of 5 cm H2O. Higher levels of PEEP may be prudent for clinically greater ventilation/perfusion mismatch or intrinsic PEEP.

Baseline hypoxemia and severity of illness affected the severity of hypoxemia during endotracheal intubation, regardless of preoxygenation technique used. However, in this analysis, baseline hypoxemia was more severe in the NIV group, suggesting that NIV may be the preferred preoxygenation technique for sicker patients with worse baseline SpO2. This analysis also underlines the importance of ensuring that intubation is achieved with the fewest attempts possible and the need for a clear plan for those with significant hypoxemia despite adequate preoxygenation.

The results of a small randomized trial (n = 52) suggests that NIV is superior to BVM with oxygen, but larger trials are needed to confirm this finding (one is ongoing).1,2 In the interim, provision of NIV as a preoxygenation technique for the sickest patients with the worst hypoxemia at baseline seems prudent.


  1. Baillard C, et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med 2006;174:171-177.
  2. Frat JP, et al. Preoxygenation with non-invasive ventilation versus high-flow nasal cannula oxygen therapy for intubation of patients with acute hypoxaemic respiratory failure in ICU: The prospective randomised controlled FLORALI-2 study protocol. BMJ Open 2017;7:e018611.