REBEL Cast Ep111: The PREPARE II Trial – Fluid Bolus Prior to Intubation?

Background:  Some of the feared complications of endotracheal intubation include hypotension, cardiac arrest, and death (cardiovascular collapse).  These complications can result from numerous causes including medication-induced vasodilation and decreased venous return to the heart due to increased intrathoracic pressure from positive pressure ventilation. In recent years there has been an increased focus on resuscitation prior to intubation in order to avoid hemodynamic complications.  One option to combat the hemodynamic effects of intubation may be administration of a fluid bolus prior to intubation.

Only one other RCT (PrePARE) [2] also examined the effects of giving a fluid bolus prior to intubation.  In this trial 337 patients were enrolled and although overall fluid bolus did not reduce the risk of cardiovascular collapse, in a subgroup analysis there was a hint of decreased risk of cardiovascular collapse among patients receiving positive pressure ventilation with a bag-mask device (OR 0.61; 95% CI 0.33 to 1.13; p = 0.03).

REBEL Cast Ep111: The PrePARE II Trial – Fluid Bolus Prior to Intubation?

Paper: Russell DW et al. Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial. JAMA 2022. PMID: 35707974 [Access on Read by QxMD]

Clinical Question: In critically ill adult patients undergoing tracheal intubation with positive pressure ventilation, does a 500cc bolus of crystalloid decrease the incidence of cardiovascular collapse (hypotension, cardiac arrest, or death)?

What They Did:

• Preventing Cardiovascular Collapse With Administration of Fluid Resuscitation During Induction and Intubation (PREPARE II)
• Multicenter, parallel group, unblinded, pragmatic, randomized clinical trial
• 11 ICUs in the US
• Patients randomized to:
  • 500mL IV fluid bolus
  • No bolus

Outcomes:

• Primary: Cardiovascular collapse
  • Defined as:
    • New or increased receipt of vasopressors or SBP <65mmHg between induction of anesthesia and 2 minutes after tracheal intubation
    • Cardiac arrest between induction of anesthesia and 1 hour after tracheal intubation
    • Death between induction of anesthesia and 1 hour after tracheal intubation
  • Secondary: Incidence of death prior to day 28

Inclusion:

• Adult patients admitted to the ICU (Age ≥18 years)
• Undergoing tracheal intubation with:
  • Medications to induce anesthesia
  • PPV with BVM or NIV between induction of anesthesia and laryngoscopy

Exclusion:

• Pregnant
• Incarcerated
• Immediate need for tracheal intubation that precluded randomization
• Clinician performing the tracheal intubation determined that administration of a fluid bolus during tracheal intubation was either required or contraindicated

Results:

• Enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation
  • 1065 (99.8%) completed the trial and included in the primary analysis
  • Median age = 62 years
  • Indication for intubation was acute respiratory failure (characterized by hypoxia, hypercarbia or both) = 60%
  • At the time of enrollment:
    • 20% of patients were receiving vasopressors
    • 10% of patients were receiving IV fluids
  • Median volume of IV fluid received between randomization and 2 minutes after tracheal intubation:
    • Fluid Bolus: 500mL (Range 300 to 500mL)
    • No Bolus: 0mL (Range 0 to 0mL)
  • In fluid bolus group most of the fluid bolus (median 300mL) was given prior to induction of anesthesia
  • Most common induction agents:
    • Etomidate: 77%
    • Ketamine: 11%
    • Propofol: 10%
  • Most common paralytic agents:
    • Rocuronium: 73%
    • Succinylcholine: 20%
  • Cardiovascular Collapse (Primary Outcome):
    • Fluid Bolus: 21.0%
    • No Bolus: 18.2%
    • Absolute difference 2.8%; 95% CI -2.2% to 7.7%; p = 0.25
    • There was no signal of benefit in any of the prespecified subgroups
  • New or Increased Receipt of Vasopressors:
    • Fluid Bolus: 20.6%
    • No Bolus: 17.6%
  • SBP <65mmHg
    • Fluid Bolus: 3.9%
    • No Bolus: 4.2%
  • Cardiac Arrest
    • Fluid Bolus: 1.7%
    • No Bolus: 1.5%
  • Death
    • Fluid Bolus: 0.7%
    • No Bolus: 0.6%
  • Death Prior to Day 28:
    • Fluid Bolus: 40.5%
    • No Bolus: 42.3%
    • Absolute Difference -1.8%; 95% CI -7.9 to 4.3%; p = 0.55

Strengths:

• Asks a clinically important question about a procedure that is commonly done
• Very few protocol violations: 99.4% of patients in fluid bolus group got their bolus and only 6 patients (1.1%) in the no fluid bolus group received a bolus
• Groups were equal at baseline in terms of approach to preoxygenation, choice of agents for induction of anesthesia/neuromuscular blockade, SBP, and O2 saturation at induction of anesthesia
• There was separation between trial groups for receipt of the intervention
• Conducted at multiple centers which increases generalizability of the results
• Randomization was appropriately performed
• Endpoints were objective and well defined

Limitations:

• Unblinded trial: Clinicians and research personnel were aware of trial group assignments after randomization
• 15% of patients were excluded due to urgency of tracheal intubation. These trial results may not generalize to patients experiencing cardiac arrest, respiratory arrest, and other highly urgent indications for tracheal intubation
• Composite outcome of differing levels of clinical importance. Most common component of the outcome was administration of new or increased vasopressor therapy. This is not the equivalent of patient death
• Trial intervention was not blinded, which could cause bias in administration of co-interventions
• Trial specifically evaluated fluid bolus prior to intubation (i.e. prophylactic) as opposed to hypotension developing during intubation (i.e. reactive)
• Only used a volume of 500mL of fluid, but it is unclear if larger volumes would end up with different results
• Patients enrolled were post-initial resuscitation and it would be interesting to know what fluid balances were prior to procedure

Discussion:

• Administration of a 500cc fluid bolus in critically ill adults undergoing tracheal intubation with positive pressure ventilation did not decrease the incidence of cardiovascular collapse compared to no fluid bolus
• The induction agents used between groups were well balanced between groups, but there is no information on the dose of the agent that was used. This is certainly a major issue as the dose of agents given can have significant impacts on hemodynamics
• RSI is a procedure that can exacerbate physiologic instability, so a targeted intervention directed at the specific pathophysiology of the patient is what is more important than just simply giving IV fluids.
• Vasopressors may be a better option to avoid hemodynamic instability resulting from RSI. Starting or titrating up vasopressors can provide a cushion for drops in blood pressure that result from intubation and can be more effective than IV fluids.

Author Conclusion: “Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse.”

Clinical Take Home Point: Putting all the evidence together (PrePARE and PrePARE II), the administration of 500mLs of fluid prior to intubation does not seem to decrease the incidence of cardiovascular collapse in critically ill adult patients undergoing tracheal intubation and should not be routine practice. “Resuscitate before you intubate” is a nuanced procedure that requires focused interventions based on the patient’s pathophysiology.

References:

1. Russell DW et al. Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial. JAMA 2022. PMID: 35707974 [Access on Read by QxMD]
2. Janz DR et al. PrePARE Investigators; Pragmatic Critical Care Research Group. Effect of Fluid Bolus on Cardiovascular Collapse Among Critically Ill Adults Undergoing Tracheal Intubation (PrePARE): A Randomised Controlled Trial. Lancet Respir Med 2019 PMID: 31585796

For More Thoughts on This Topic Checkout:

• REBEL EM: PrePARE – Effect of Fluid Bolus on CV Collapse During RSI

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)