Effect of fluid bolus administration on cardiovascular collapse among critically ill patients undergoing tracheal intubation: a randomized clinical trial
Russell DW, Casey JD, Gibbs KW, et al. JAMA. Published online June 16, 2022. doi:10.1001/jama.2022.9792
Hypotension is common during intubation of critically ill patients, occurring in an estimated 25% to 40% of patients in the ICU undergoing rapid sequence intubation.
Current international guidelines and expert recommendations suggest giving IV fluids peri-intubation. A prior RCT (Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation; PREPARE) in approximately 300 patients did not find an overall difference in cardiovascular collapse with the use of IV fluids, but did find a benefit in a hypothesis-generating subgroup analysis of patients receiving bag-valve-mask ventilation or noninvasive ventilation.
That finding set the stage for the current PREAPRE II trial.
This was a multicenter, unblinded pragmatic RCT from 11 ICUs across the U.S. comparing a 500-cc bolus of isotonic fluid vs no bolus peri-intubation. No other aspects of the intubation were protocolized.
The study included adults receiving rapid sequence intubation who were also receiving either bag-valve-mask ventilation or noninvasive ventilation, and excluded patients who could not wait until randomization or who had a contraindication to receiving fluids.
The primary outcome was cardiovascular collapse, which was a composite outcome of (1) new or increased vasopressors between induction and 2 minutes after intubation, (2) systolic blood pressure <65 mm Hg between induction and 2 minutes after intubation, (3) cardiac arrest between induction and 1 hour after intubation, or (4) death between induction and 1 hour after intubation.
The study enrolled 1,065 patients with a median age of 62 years; 42.1% were women, and 20% had already been given vasopressors.
The agents used for sedation and paralysis were similar between groups (mostly etomidate and rocuronium), as were the initial vital signs and indications for intubation.
Cardiovascular collapse occurred in 21.0% of the fluid group vs 18.2% of the no-fluid group; almost all events involved new/increased vasopressors and hypotension.
The secondary outcomes, including death at 28 days, were also similar across groups (40.5% vs 42.3%).
Overall, this was a well-conducted trial with concealment of group assignment until the time of intubation to minimize selection bias. However, the trial was nonblinded and has the further limitations of using a composite outcome with very different levels of severity, and excluding 15% of intubations because of urgency, thus functionally excluding the most ill patients.
Because the median systolic blood pressure at induction was 128 mm Hg, the findings cannot be extrapolated to hypotensive patients, or patients being intubated for cardiac or respiratory arrest or other emergent conditions.
EDITOR’S COMMENTARY: Contradicting previous research and several professional-society guidelines on the topic, the authors of this multicenter randomized trial found no benefit from a pre/peri-intubation 500-cc fluid bolus on the incidence of cardiovascular collapse during urgent intubations of ICU patients receiving bag-valve-mask ventilation or noninvasive ventilation during the procedure. Importantly, although not mentioned in the title, abstract, or discussion, we can’t apply the findings to hypotensive or crashing patients, because these patients were not included in the study.