Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation

@DerekRussellMD. JAMA; 328(3):270-279. doi:10.1001/jama.2022.9792

Clinical Question

  • In critically ill adult patients undergoing tracheal intubation and positive pressure ventilation, does intravenous infusion of a 500ml fluid bolus vs no fluid bolus, decrease the incidence of cardiovascular collapse during, or shortly after the procedure?


  • Tracheal intubation in the intensive care unit is a common intervention that entails significant risk
  • Haemodynamic instability, in the form of hypotension, increased vasopressor requirement or cardiac arrest, is a common complication, occurring in around 25% of intubations in the critical care setting, compared with only 4% in the theatre setting
  • There are a number of potential causes, including loss of sympathetic tone, increased intrathoracic pressure and the use of anaesthetic induction agents
  • A simple potential intervention would be a fluid bolus to increase intravascular filling
  •   The only prior study on this intervention was PREPARE, which was stopped early due to futility
  • A post hoc subgroup analysis of PREPARE found a potential benefit in patients undergoing positive pressure ventilation during the intubation process


  • Multi-centre, randomised, unblinded trial
  • 1:1 randomisation to intervention and control in randomly permuted block sizes of 2, 4 and 6; stratified by trial site
  • Informed consent was obtained after the intervention
  • Sample size calculation: 1065 patients would give 80% power to detect a between group relative difference of 35%
  • Primary outcome was cardiovascular collapse, defined as one or more of:
    • New or increased receipt of vasopressors between induction and 2 minutes after tracheal intubation
    • Systolic blood pressure of less than 65 mmHg between induction and 2 minutes after tracheal intubation
    • Cardiac arrest between induction and 1 hour after tracheal intubation
    • Death between induction and 1 hour after tracheal intubation
  • Sole pre-specified secondary outcome was in-hospital mortality by day 28


  • 11 intensive care units in the US
  • Enrollment occurred between February 2019 and May 2021
  • Enrollment paused between February 2020 and August 2020 due to Covid-19 pandemic


  • Inclusion:
    • Adult patients over 18 years old
    • Undergoing tracheal intubation, with a plan to use
      • Anaesthetic induction agents
      • Positive pressure ventilation during induction and prior to direct laryngoscopy
  • Exclusion:
    • Immediate need for intubation
      • These cases were deemed too urgent to allow time for randomisation
    • If the intubating clinician felt the intervention was either indicated or contra-indicated
    • Pregnancy
    • Incarceration
  • 1576 patients screened
    • 1065 randomised
      • 538 fluid bolus
      • 527 no fluid bolus
  • Comparing baseline characteristics of fluid bolus vs. no fluid bolus group
    • Median age (years): 61 vs 62
    • Female Sex (%): 41 vs 43
    • BMI (kg/m²): 28 vs 28
    • Comorbidities (%):
      • Diabetes: 26 vs 29
      • Hypertension: 34 vs 34
      • COPD: 19 vs 17
      • Congestive cardiac failure: 15 vs 14
      • Renal failure: 4 vs 6
    • Indications for intubation (%)
      • Hypoxia: 41 vs 43
      • Hypercarbia: 7 vs 8
      • Hypoxia and hypercarbia: 11 vs 11
      • Low GCS: 20 vs 20
    • Use of vasopressors (%): 20.0 vs 19.4
    • Receiving IV fluids at enrollment (%): 10.2 vs 9.9


  • Fluid bolus group
    • 500mls of isotonic crystalloid solution, intravenously
    • Aim to infuse as much as possible of the 500mls before induction of anaesthesia, without delaying tracheal intubation
    • Complete infusion of any remaining fluid after induction, during tracheal intubation


  • No fluid bolus group
    • Initiation of fluid bolus not permitted, except
      • As treatment for hypotension
      • If operator determined that fluid bolus was necessary for patient safety

Management common to both groups

  • All other aspects of care at clinicians’ discretion
  • Specifically
    • Ongoing IV fluid infusions could be continued
    • Vasopressors to treat hypotension
    • Choice of induction agent


  • Primary outcome: incidence of cardiovascular collapse – no significant difference
    • 21.0% in fluid bolus group vs 18.2% in no fluid bolus group
      • Absolute difference 2.8%, 95% CI -2.2% to 7,7%
  • Secondary outcome: in-hospital mortality at 28 days – no significant difference
    • 40.5% in fluid bolus group vs 42.3% in no fluid bolus group
  • No difference in any of the prespecified exploratory outcomes

Authors’ Conclusions

  • In critically ill adults undergoing tracheal intubation with positive pressure ventilation, a fluid bolus during induction of anaesthesia did not decrease the incidence of cardiovascular collapse, compared with no fluid bolus


  • Pragmatic, randomised design
  • Clinically relevant question with an easily implemented intervention
  • Conclusions seem to be broadly generalisable, with patient characteristics that seem very similar to patients on my unit
    • Co-morbidities
    • Acute presentation
    • Indications for intubation
  • Use of composite outcome increases probability of finding a clinically important difference
  • Very impressive implementation of interventions, and separation between the two groups
    • 99.4% of fluid bolus group received bolus, compared with 1.1% in no fluid bolus group
    • Median of 500mls of fluid administered in fluid bolus group at 2 minutes after intubation, compared with 0mls in no fluid bolus group
    • Lowest volume administered was 300mls
  • Only a small variation in fluid management between the the two groups following induction
    • A large variation could have introduced bias


  • One could argue that fluid administration does not address the main causes of cardiovascular collapse during intubation
    • i.e. the hypothesis lacks face validity
  • The selection of induction agents is not representative of the agents used in most units outside the US
  • Issues with using a composite outcome:
    • The components of the composite outcome are not all equally important
      • for example, cardiac arrest is devastating compared to an episode of hypotension
    • The components of the composite outcome are not all patient-centred
      • patients unlikely to be effected by an episode of hypotension or increased dose of vasopressor
    • Some elements of the composite outcome susceptible to bias
      • Operators’ use of vasopressors may be affected by the trial intervention
      • Increased use of vasopressors may not reflect genuine cardiovascular collapse or hypotension
  • Unblinded trial – could it have been possible, albeit more difficult, to blind clinicians to the intervention?
  • Large proportion of patients (15%) were excluded due to urgency – potential cause of bias

The Bottom Line

  • The routine administration of isotonic crystolloid solution during induction of anaesthesia and intubation does not reduce the incidence of cardiovascular collapse
  • I will continue to assess my patients’ fluid status on a case by case basis, and will only administer a fluid bolus in patients who display convincing evidence of hypovolaemia
  • I will continue to proactively administer a dose of vasopressor during induction in patients who I consider at particular risk of cardiovascular collapse

External Links


Summary author: Omar Jundi – @bi0marker
Summary date: 16/12/2022
Peer-review editor: David Slessor

Picture by: author/site


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