By Betty Tran, MD, MSc
Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago
SYNOPSIS: In this randomized pragmatic clinical trial, a peri-intubation intravenous fluid bolus administered to critically ill adults undergoing tracheal intubation with positive pressure ventilation did not significantly reduce the risk of cardiovascular collapse.
SOURCE: Russell DW, Casey JD, Gibbs KW, et al. Effect of fluid bolus administration on cardiovascular collapse among critically ill patients undergoing tracheal intubation: A randomized clinical trial. JAMA 2022;328:270-279.
Endotracheal intubation can result in hypotension due to medication-related vasodilation and decreased venous blood return to the heart because of increased intrathoracic pressure with positive pressure ventilation. Some international anesthesia-based organizations have included an intravenous (IV) fluid bolus into their algorithms to optimize hemodynamics prior to and during intubation.1-2 The Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II) trial sought to answer the question of whether an IV fluid bolus decreased the incidence of cardiovascular collapse in critically ill adults undergoing tracheal intubation with positive pressure ventilation.
This was a multicenter, parallel-group, pragmatic, unblinded, randomized trial performed in 11 intensive care units (ICUs) in the United States. Eligible patients were critically ill adults receiving anesthesia-inducing medications for intubation and who received positive pressure ventilation with bag-mask or a noninvasive ventilator between induction of anesthesia and laryngoscopy. The primary outcome was cardiovascular collapse defined as one or more of the following: new or increased vasopressor requirement between induction of anesthesia and two minutes after tracheal intubation, systolic blood pressure < 65 mmHg between induction of anesthesia and two minutes after tracheal intubation, cardiac arrest between induction of anesthesia and one hour after tracheal intubation, or death between induction of anesthesia and one hour after tracheal intubation. The secondary outcome was death prior to 28 days (censored for hospital discharge). Because this was a pragmatic trial, patients could continue receiving IV fluids initiated prior to enrollment and could receive a fluid bolus for hypotension after induction of anesthesia. All aspects of tracheal intubation (e.g., induction agents, need for vasopressors) were deferred to the operator.
Overall, 1,065 patients were analyzed, 20% of whom were receiving vasopressors and 10% were receiving IV fluids at the time of enrollment. Additionally, 12.3% of patients in the fluid bolus group and 11.8% in the no fluid bolus group received a vasopressor between enrollment and induction of anesthesia to prevent hypotension. There was no significant difference in cardiovascular collapse between the fluid bolus group (21.0%) and the no fluid bolus group (18.2%) (absolute difference 2.8%; 95% confidence interval [CI], -2.2% to 7.7%; P = 0.25). There also was no significant difference in mortality at 28 days between the fluid bolus group (40.5%) and the no fluid bolus group (42.3%) (absolute difference -1.8%; 95% CI, -7.9% to 4.3%; P = 0.55). In terms of exploratory outcomes, there were no differences between the groups in terms of each component of the composite cardiovascular collapse definition, minimum level and change in level of systolic blood pressure, lowest oxygen saturation and percentage of oxygenation saturation < 80%, days off invasive mechanical ventilation through 28 days, and days out of intensive care through 28 days.
COMMENTARY
Unless otherwise contraindicated, a fluid bolus peri-intubation seems physiologically beneficial given the effects of anesthesia-inducing medications and particularly positive pressure ventilation on systemic blood pressure. Although this recommendation has been incorporated into some international ICU tracheal intubation guidelines, this current study as well as a prior trial have not shown benefit.
The first Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation Before Tracheal Intubation (PREPARE) trial was the first randomized trial comparing a fluid bolus before induction to no fluid bolus in critically adults undergoing tracheal intubation.3 Similar to PREPARE II, it also was a multicenter, unblinded, and pragmatic trial with a primary outcome of cardiovascular collapse defined similarly. Ultimately, 537 patients were randomized, with no significant difference between the fluid bolus and no fluid bolus groups regarding cardiovascular collapse, the individual components in the composite primary outcome, or in-hospital mortality. However, positive pressure ventilation appeared to be an effect modifier in this trial; for patients receiving bag-mask ventilation or noninvasive ventilation, there was a trend toward benefit of a fluid bolus in reducing the incidence of cardiovascular collapse (0.61; 95% CI, 0.33-1.13; P = 0.0080, and 0.51; 95% CI, 0.24-1.09; P = 0.032, respectively). Interestingly, in patients not receiving positive pressure ventilation, a fluid bolus appeared to actually increase the risk of cardiovascular collapse. These findings subsequently prompted PREPARE II, the results of which are presented here.
Based on these two studies, a peri-intubation IV fluid bolus does not benefit patients undergoing intubation in the ICU in terms of preventing cardiovascular collapse, even in those receiving positive pressure ventilation after induction of anesthesia. It may be that the overall volume of crystalloid may be inadequate (the study reported that the majority of the bolus was given before induction of anesthesia), but it also is plausible that fluids alone are not the answer to improving pre-intubation hemodynamics after anesthesia induction, especially since 20% of patients already were receiving vasopressor support pre-intubation in PREPARE II. Future studies could be directed to exploring whether routine vasopressor use may attenuate the hypotensive response or the optimal choice and dose of induction medications.
REFERENCES
- Higgs A, McGrath BA, Goddard C, et al. Guidelines for the management of tracheal intubation in critically ill adults. Br J Anaesth 2018;120:323-352.
- Quintard H, I’Her E, Pottecher J, et al. Experts’ guidelines of intubation and extubation of the ICU patient of French Society of Anaesthesia and Intensive Care Medicine (SFAR) and French-speaking Intensive Care Society (SRLF): In collaboration with the pediatric Association of French-speaking Anaesthetists and Intensivists (ADARPEF), French-speaking Group of Intensive Care and Paediatric emergencies (GFRUP) and Intensive Care physiotherapy society (SKR). Ann Intensive Care 2019;9:13.
- Janz DR, Casey JD, Semler MW, et al. Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): A randomised controlled trial. Lancet Respir Med 2019;7:1039-1047.
