PREOXI Trial – Noninvasive Ventilation for Preoxygenation

Noninvasive Ventilation for Preoxygenation during Emergency Intubation

Gibbs KW. N Engl J Med 2024;390:2165-77. DOI:10.1056/NEJMoa2313680

Clinical Question

  • In critically ill patients undergoing tracheal intubation does pre-oxygenation with non-invasive ventilation compared with pre-oxygenation with an oxygen mask reduce the incidence of hypoxemia during intubation?

Background

  • Emergency intubation in the emergency department or ICU is common with >2 million events in the USA/year
  • Emergency intubation is associated with high adverse event rate, thought to be up to 40% in this cohort compared with ~2% of operating theatre intubations
  • Hypoxemia is a common event and is associated with cardiac arrest in emergency intubation
  • Pre-oxygenation denitrogenates the functional residual capacity of the lung, effectively giving a buffer during the apnoeic period following induction of anaesthesia
  • There has been some concern that using BiPAP or other forms of positive non-invasive ventilatory support in the pre-oxygenation and apnoeic phase, can insufflate the stomach and increase the risk of aspiration
  • There is limited evidence to date as to which pre-oxygenation technique is best

Design

  • The PRagmatic trial Examining Oxygenation prior to Intubation (PREOXI trial) hypothesised that use of BiPAP for pre-oxygenation would reduce the chance of hypoxia during urgent intubation
  • Multi-centre, pragmatic, randomised controlled trial
  • 1:1 randomisation, with allocation concealment (sequentially numbered opaque envelopes)
  • Randomisation was stratified to site with permuted blocks of variable sizes
  • No blinding
  • Delayed consent

Setting

  • 24 sites: 7 emergency departments and 17 ICUs in the USA, in 15 different hospitals
  • Operators had performed a median of 50 previous tracheal intubations
  • The trial ran between March 2022 and October 2023

Population

  • Inclusion:
    • Those requiring urgent intubation
    • > 18 years
    • The intubation involved the use of sedation and laryngoscopy
  • Exclusion:
    • Known to be pregnant
    • Known to be a prisoner
    • Were already receiving positive-pressure ventilation
    • Had apnoea or hypopnoea
    • Had an immediate need for tracheal intubation that precluded randomization
    • Patients were also excluded if the clinician performing the procedure (referred to as the “operator”) determined that preoxygenation with noninvasive ventilation was contraindicated
  • A sample size of 1264 was deemed necessary to detect a difference of 6% in the primary outcome (85% statistical power, and a two-sided alpha level of 0.05). This was increased to 1300 to ensure adequate power if data was missing
  • A total of 4567 patients were assessed for eligibility, of whom 1301 were randomised. The main reasons for exclusion were urgent intubation with no time for randomisation (924), already on NIV (840) or vomiting, hematemesis, hemoptysis, or epistaxis (389) excluding the use of NIV
  • Comparing baseline characteristics of intervention vs. control group
    • The groups were well matched at baseline
    • The median age was 61 years, 39.6% were female, BMI was 27.6 vs 26.6, intubation was in the ICU in 73.8% vs 72.6% of cases (the rest in the emergency room), median APACHE II was 17
    • In the hour before intubation, 27.6% vs 27.1% were on vasopressors, 23.3% vs 25.2% were on HFNO, 58.9% vs 58.7% had an FiO2:SaO2 <315.

Intervention

  • 645 patients were randomised to the NIV group
    • BiPAP was applied during pre-oxygenation for a minimum of 3 minutes. FiO2 100%, EPAP > 5cm H20, IPAP >10cm H2O, respiratory rate >10/minute
    • 616 received preoxygenation with NIV, 22 received preoxygenation with oxygen mask, 7 received another device
    • During interval between induction & initiation of laryngoscopy 88.1% received positive pressure ventilation

Control

  • 656 were randomised to the oxygen mask group
    • Operators were instructed to use a non-rebreather mask or bag mask O2 device without manual ventilation
    • Various combination of techniques were applied (in some cases patients got more than one different technique), most commonly a non-rebreather mask (87.7%), HFNO (12.2%), Bag mask O2 without ventilation (13.7%), Bag mask O2 with ventilation (1.2%). 4 patients received NIV
    • During interval between induction & initiation of laryngoscopy 31.1% received positive pressure ventilation (includes noninvasive ventilation and bag-mask ventilation – patients could receive both, either or none)

Management common to both groups

  • The agents used for induction were at the discretion of the operator
  • Patient positioning was at the discretion of operator
  • Ventilation with a bag-mask or NIV after induction of anaesthesia and/or apnoeic oxygenation allowed at discretion of operator

Outcome

  • Primary outcome: The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anaesthesia and 2 minutes after tracheal intubation
    • In the NIV group, 57 of 624 patients (9.1%) and in the oxygen-mask group 118 of 637 patients (18.5%) developed hypoxemia (difference, −9.4% 95% CI, −13.2 to −5.6; P<0.001)
    • NNT =11
  • Secondary outcomes:
    • In the NIV group, 39 of 624 patients (6.2%) and in the oxygen-mask group 84 of 637 patients (13.2%) developed hypoxemia with SaO2 <80% (difference, −6.8% 95% CI, −10.2 to −3.7)
    • In the NIV group, 39 of 624 patients (2.4%) and in the oxygen-mask group 84 of 637 patients (5.7%) developed hypoxemia with SaO2 <70% (difference, −3.2% 95% CI, −5.4 to −1.1)
    • Cardiac arrest between induction of anaesthesia and 2 minutes after tracheal intubation occurred in 1/645 patients (0.2%) in the NIV group and in 7/656 patients (1.1%) in the oxygen-mask group (difference, −0.9%; 95% CI, −1.8 to −0.1)
    • New or increased use of vasopressors 17.2% (NIV group), 17.8% (mask group)
    • SBP <65mmHg 2.9% (NIV group) vs 4.4% (mask group)
  • Subgroup Analysis:
    • All pre-specified subgroups favoured NIV (high BMI, intubation in the ICU, those with hypoxemic respiratory failure as cause of intubation, FiO2 in hour before intubation, high APACHE II scores)
  • Safety:
    • Aspiration as assessed by clinical, physiological and radiological variables: 6 of 645 patients (0.9%) in the NIV group and in 9 of 656 patients (1.4%) in the oxygen-mask group

Authors’ Conclusions

  • “In this trial involving critically ill adults undergoing tracheal intubation in an emergency department or an ICU, the incidence of hypoxemia was lower with preoxygenation with noninvasive ventilation than with an oxygen mask”

Strengths

  • Pragmatic design, allocation concealment, intention to treat analysis,
  • Data available for primary outcome in 624/645 in NIV group and 637/656 in mask group
  • Multiple sites improves generalisability
  • Large Sample Size improves power
  • Heterogeneity Analysis
  • Data collection by independent assessor

Weaknesses

  • 20% of patients were excluded due to already being on NIV. However, it is completely reasonable to exclude this group
  • Hypoxemia is a surrogate outcome, but IS reliable and correlates with clinically important outcomes, eg cardiac arrest
  • The control arm would not be usual practice in many centres. The use of a NRBM seems to be particular to the USA. My understanding is that in Australia and the UK, the most common pre-oxygenation technique would be BVM device often with a PEEP valve, or a Mapleson C circuit and manual ventilation during apnoea. HFNO is another commonly used technique for pre-oxygenation. The external validity is thus questionable
  • During the apnoeic period, ventilation was not mandated. Again this differs from my usual practice making these results difficult to apply to my practice.
  • Consideration of plastic waste and cost should be considered if a BiPAP circuit is used for just a few minutes prior to intubation

The Bottom Line

  • This is a very thought provoking study and challenges my usual practice
  • I will be more likely to use BiPAP when intubating critically ill patients
  • However, the control group (mostly pre-oxygenation with a NRBM) in this trial does not reflect usual practice in my institution, so it is difficult to apply these results to my practice

External Links

Metadata

Summary author: Celia Bradford @celiabradford
Summary date: July 3 2024
Peer-review editor: david slessor

 

 

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