Rapid sequence intubation is used in critically ill patients who have not been fasted and are presumed to have higher risk for aspiration and vomiting. During RSI, there is a period of 45-60 seconds between the induction with a sedative and paralytic and the first intubation attempt. It is generally taught that ventilations are contraindicated during this period because they increase the risk of aspiration. However, apparently that recommendation is based on research that involved listening to the stomachs of healthy volunteers with a stethoscope as a (I would think very poor) surrogate for aspiration. (Casey 2019) (I haven’t read the original papers yet myself, but this seems very funny.) Furthermore, the rate of aspiration is actually very low in RSI. Therefore, the PreVent trial was run to examine this practice.
PreVent: Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. The New England journal of medicine. 2019; 380(9):811-821. PMID: 30779528 [paid full text]
This is a multicenter, parallel-group, unblinded, pragmatic, randomized trial comparing bag-mask ventilation with no ventilation during the interval between induction (administration of a sedative medication) and laryngoscopy during tracheal intubation of critically ill adults.
Adult patients (18 and older) undergoing intubation at one of 7 academic ICUs in the USA.
Exclusions: Pregnancy, incarceration, immediate need for intubation precluding randomization, or if the clinician thought that ventilations between induction and intubation attempt were either required or contraindicated.
Ventilations using a BVM in the period between induction and the first intubation attempt. Education was provided, and ventilation was supposed to be done with a PEEP valve set between 5 and 10 cm of water, an oropharyngeal airway in place, with a two handed grip, and ventilations at a rate of 10 per minute and with the smallest volume required to generate a visible chest rise.
Ventilations were not allowed between induction and the first intubation attempt, unless the oxygen saturation dropped below 90% or the treating physicians thought it was required for some other reason.
The primary outcome was the lowest oxygen saturation seen between induction and 2 minutes after intubation.
401 patients were included, out of 667 screened. 97 patients were excluded because the clinicians thoughts they needed ventilation. 51 were excluded because the clinicians thought ventilation was contraindicated. (This is really important information, and it drives me nuts that it is hidden in a supplementary appendix.)
The groups were not treated the same prior to induction. More patients in the BVM group had BVM used for pre-oxygenation (40% vs 10%). However, the median oxygen saturation at induction was the same in both groups, and the number of patients with an oxygen saturation below 92% was a little higher in the BVM group (14% vs 9%).
Most of the groups got the management assigned to them (99.5% of the ventilations group got ventilations, and only 2.5% of the no-ventilations group were ventilated prior to an intubation attempt).
For the primary outcome, the median lowest oxygen saturation was 96% in the BVM group and 93% in the no-ventilations group (p=0.01).
An oxygen saturation of less than 80% occurred in 11% of the BVM ventilation group and 23% of the no-ventilation group (relative risk, 0.48; 95% CI, 0.30 to 0.77). Both of these numbers are much too high. Desaturations below 90% were also lower in the BVM ventilation group (30 vs 40%).
There was no difference in aspiration, whether reported at time of intubation (2.5% vs 4%), or based on 48 hours chest x-ray (16% vs 15%).
There was no difference in oxygen requirement, in-hospital mortality, or ventilator free days. (In hospital mortality was 35% in both groups.)
My guess is that this paper will change practice for a lot of people. I am of mixed feelings about that. On the one hand, the ban on ventilations doesn’t seem to be well supported by the literature. On the other hand, there are multiple issues with this study that make extrapolation of the results difficult.
The primary outcome, although statistically significant, is not clinically meaningful. There is no real clinical difference between a saturation of 96% and 93%. However, focusing on the median is a mistake. There are clearly more patients with very low oxygen levels in the no ventilation group.
It is important to remember that oxygen saturation is a surrogate outcome. What we really care about is keeping people alive with good neurologic function. Oxygen saturation is a decent surrogate outcome, with a strong association with important outcomes. (Mort 2004; De Jong 2017) However, not everyone with a desaturation will have a patient oriented outcome, which must be considered when trying to determine the overall harms and benefits of this intervention.
It is reassuring that there was no difference in aspiration in this group, but aspiration is a difficult entity to define accurately, is relatively rare, and is also a surrogate. In a relatively small, non-blinded trial, we could be misled by the aspiration numbers. The trial was underpowered for massive aspiration events, which could easily be worse than a transient desaturation (if, for example, one led to a can’t intubate, can’t oxygenate scenario). Furthermore, the harms from aspiration might come in the form of a pneumonia 1 week out, which wasn’t looked for in this study.
Moving beyond the various surrogate outcomes, there were no differences in any of the patient oriented outcomes measured (such as mortality or time spent on a ventilator).
Clinicians could exclude patients who they felt either required or could not have ventilations, which introduces bias. (Interestingly, although the groups are unbalanced, it is in the opposite direction of what I would have expected. There were more GI bleed patients in the ventilations group and more patients with pneumonia and hypercarbic respiratory failure in the no-ventilation group). Ultimately, these exclusions mean you should not just apply these results to all comers, but instead apply clinical judgement first, like was done here. (Even if we aren’t sure that judgement is based on anything.)
Preoxygenation was not the same in both groups, and overall, I think it was pretty poor quality. 10% of these patients were preoxygenated with nasal prongs alone! Another 2.5% had no preoxygenation at all. A nonrebreather is a great tool for preoxygenation, but only when used at flush rate. (Driver 2016) It isn’t clear if the 30% of patients preoxygenated with a nonrebreather had adequate flow rates. (My guess is no.) Ultimately, the poor preoxygenation led to 10% of patients with an oxygen saturation less than 92% at induction, which is simply not good enough. Furthermore, the lowest oxygen saturations allowed in the paper are much too low, with 16.5% of patients allowed to drop below 80%. (For what it’s worth, apneic oxygenation was also more common in the BVM group – 100% vs 77%).
Better pre-oxygenation and re-oxygenation could significantly impact the results of this study. If you don’t let patients desaturate, both because they are better pre-oxygenated, and because you are quicker to stop an intubation attempt and re-oxygenate, then it isn’t clear that a few ventilations prior to intubation could possibly help.
In contrast to the poor pre-oxygenation they describe, the BVM technique here was perfect. They held training sessions and emphasized a 2 handed BVM seal, with a PEEP valve set between 5 and 10 cm water, with ventilations at 10 breaths a minute with the smallest volume required to see chest rise. (Whether this technique was actually followed is unclear). My concern is that BVM is a difficult skill, and its use in the real world is frequently quite divergent from the ideal technique described here. With worse BVM technique, we might see very different results.
My focus will still be great pre-oxygenation, denitrogenation, and maximized first pass success, with a clear backup plan. However, in select patients at higher risk of desaturation, and with low risk of aspiration, I will probably include perfect technique BVM ventilations as part of my RSI.
Other PreVent FOAMed
Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. The New England journal of medicine. 2019; 380(9):811-821. PMID: 30779528
De Jong A, Rolle A, Molinari N, et al. Cardiac arrest and mortality related to intubation procedure in critically ill adult patients: a multicenter cohort study. Crit Care Med 2018; 46: 532-9.
Driver BE, Prekker ME, Kornas RL, Cales EK, Reardon RF. Flush Rate Oxygen for Emergency Airway Preoxygenation. Annals of emergency medicine. 2017; 69(1):1-6. PMID: 27522310
Mort TC. The incidence and risk factors for cardiac arrest during emergency tracheal intubation: a justification for incorporating the ASA Guidelines in the remote location. J Clin Anesth 2004; 16:508-16.
Morgenstern, J. PreVent: BVM during RSI (Casey 2019), First10EM, April 1, 2019. Available at: