End-Tidal Oxygen for Intubation in the Emergency Department (PREOXED)

August 27, 2024 updated by: Matthew Oliver, Sydney Local Health District

Preoxygenation Using End-Tidal Oxygen for Rapid Sequence Intubation in the Emergency Department (The PREOXED Trial) - A Multicentre Stepped Wedge Cluster Randomised Control Trial

Rapid Sequence Intubation (RSI) is a high-risk procedure in the emergency department (ED). Patients are routinely preoxygenated (given supplemental oxygen) prior to RSI to prevent hypoxia during intubation. For many years anaesthetists have used end-tidal oxygen (ETO2) levels to guide the effectiveness of preoxygenation prior to intubation. The ETO2 gives an objective measurement of preoxygenation efficacy. This is currently not available in most EDs.

This trial evaluates the use of ETO2 on the rate of hypoxia during intubation for patients in the ED.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND AND INTRODUCTION

Rapid Sequence Intubation (RSI) is a common procedure in Emergency Departments (ED). However, it is a high-risk procedure and is associated with significant complications including hypoxia, failed intubation, hypotension, trauma and aspiration. (1-3) Specifically, hypoxia during intubation can lead to poor outcomes such as dysrhythmias, haemodynamic compromise, hypoxic brain injury and death and therefore oxygen desaturation is of primary concern during any intubation procedure. (4, 5) In order to prevent desaturation events during intubation, a number of steps are taken by clinicians. These include optimal patient positioning, adequate preoxygenation, assessment of airway anatomy and development of a detailed airway plan as well as the use of apnoeic oxygenation.(6)

Effective preoxygenation is vital to ensure that the patient does not develop hypoxia during the period between induction (administration of sedative and paralytic agents) and restoration of ventilation by successful endotracheal intubation or rescue breathing. Various methods of preoxygenation have been developed to wash the nitrogen out of the lungs (denitrogenation) which allows the functional residual capacity (FRC) to act as an oxygen reservoir during intubation, which prolongs safe apnoea time, therefore, preventing desaturation whilst an endotracheal tube (ETT) is placed.

Adequate preoxygenation is especially important for those patients at highest risk of hypoxia during the RSI. This patient group includes those with underlying lung pathology e.g. pneumonia, patients with increased metabolic demand e.g. sepsis, patients with an oxygen requirement prior to RSI, or patients with underlying conditions that predisposes to hypoxia e.g. obesity.

For many years anaesthetists have used end-tidal oxygen (ETO2) levels to guide the effectiveness of preoxygenation. ETO2 measures the exhaled oxygen concentration and is a marker of the oxygen concentration in the alveoli. Prior to induction, anaesthetists most commonly preoxygenate with a face-mask seal via either a circle circuit, Mapleson circuit, or bag valve mask. ETO2 provides an objective measurement of preoxygenation efficacy. The Difficult Airway Society guidelines suggest aiming for an ETO2 of ≥87% prior to commencing RSI.(7) ETO2 levels are not routinely measured in Emergency Departments.

Currently, it is not possible to measure the effectiveness of preoxygenation in the ED. Pulse-wave oximetry reflects peripheral oxygen saturation and not the pulmonary oxygen concentration. Therefore, to attempt to optimize preoxygenation the emergency clinician currently can only use time as a surrogate. The typically recommended duration of preoxygenation is > 3 minutes.

Recently, the investigators conducted two multi-site studies (Ethics identifier: 2019/ETH06644) that investigated the use of ETO2 in the ED.(8, 9) The first study was conducted with clinicians blinded to the ETO2 result (8). The investigators demonstrated that preoxygenation was uniformly poor with only 26% of patients achieving the required target ETO2 of ≥85%. The investigators then completed a second study where clinicians had access to ETO2 values and found that the proportion of patients reaching levels ≥85% was improved to 67% of patients. (9) The prevalence of hypoxemia (SpO2 <90%) in the group blinded to ETO2 was 18% (n=18, 95% CI: 11% to 27%) and was 8% in the group where ETO2 was available (n = 8, 95% CI: 4% to 15%). These studies indicate that the use of ETO2 may substantially improve preoxygenation in the ED and therefore reduce the risk of hypoxia.

These studies, however, were focused on preoxygenation practices and not patient-oriented outcomes (hypoxia) and were limited in design and resources. Consequently, it is still unclear whether the use of ETO2 in the ED leads to improved clinical outcomes.

RATIONALE FOR PERFORMING THE STUDY

The aim of this study is to determine the effectiveness of ETO2 monitoring in preventing desaturation for patients with a high risk of hypoxia undergoing RSI in ED.

HYPOTHESIS

The investigators hypothesise that the use of ETO2 monitoring leads to reduced rates of oxygen desaturation during the peri-intubation period compared to when it is not used.

Study Type

Interventional

Enrollment (Estimated)

1400

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55451
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Not yet recruiting
        • University of New Mexico Medical Center
        • Contact:
    • New York
      • Bronx, New York, United States, 10451

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The patient is located in the ED resuscitation bay of the participating centre.
  2. The planned procedure is orotracheal intubation using a laryngoscope and RSI technique with preoxygenation for patients who are spontaneously breathing.

  3. The patient is deemed to be at a high risk of hypoxia during RSI as per the treating ED clinician, as defined by:

    • Any patient requiring any form of oxygen therapy before preoxygenation.

    • Any patient with respiratory pathology based on clinical or radiological findings. Including, but not limited to:

      • Pneumonia, pulmonary oedema, acute respiratory distress syndrome (ARDS), aspiration, pulmonary contusion from trauma, infective exacerbations of known lung disease (e.g. asthma, pulmonary fibrosis, emphysema) or pulmonary embolism (PE)

    • Any patient with high oxygen consumption. Including, but not limited to:

      • Sepsis, Diabetic ketoacidosis, alcohol or drug withdrawal, seizures, thyrotoxicosis

    • Any underlying patient condition that may predispose to hypoxemia. Including, but not limited to:

      • Obesity, pregnancy, underlying lung disease (e.g. asthma, pulmonary fibrosis, emphysema), severe injury- hypovolaemia/haemorrhage.
    • or any other patient that the treating clinician has a high concern for hypoxemia during RSI.

Exclusion Criteria:

  1. Patient is known to be less than 18 years old.
  2. The patient has a supraglottic device in-situ e.g iGel or LMA.
  3. The patient is known to be pregnant.
  4. The patient is known to be a prisoner.
  5. The patient was intubated in the prehospital environment.
  6. Immediate need for tracheal intubation precludes preoxygenation i.e. the patient is in cardiac arrest.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control period
The control period includes a period whereby clinicians will not have access to ETO2 monitoring and routine RSI practices will be documented including all study variables. At all institutions, RSI is performed in a similar manner, utilising an airway checklist. There is no 'standard operating procedure' for RSI in any of the EDs and methods, therefore, vary depending on clinician preference and the condition of the patient, however, each site is a tertiary-level, university teaching hospital and therefore clinical practice is up to date and evidence-based. Standard preoxygenation methods in the Emergency department often consist of a bag-valve mask, with or without a PEEP valve, set at 15L/min, or the use of non-invasive ventilation or a non-rebreather mask, with or without a nasal cannula, set at 15 L/min or flush rate oxygen (>40 L/min). US sites have access to high-flow (>30L/min) oxygen. This is the only difference in the preoxygenation method.
Experimental: Study period

For all patients involved in the study, the only intervention will be the use of ETO2 to guide preoxygenation. All aspects of RSI will be at the discretion of the treating clinician including sedative/paralytic medications, positioning of the patient, preoxygenation method, intubation techniques and post-intubation sedation.

Clinicians will be encouraged to aim for the highest ETO2 result possible with a goal of >85%. Clinicians will be able to view the ETO2 values and can decide on any changes to the preoxygenation techniques if deemed necessary. These techniques may include improved patient positioning, improved face mask seal, increased oxygen flow, length of preoxygenation time, or altering the preoxygenation device.
Device: End-tidal oxygen monitor

The only additional equipment required for this study is the Philips™ IntelliVue G7m Gas Analyser Module 866173. This provides a non-dispersive infrared measurement of respiratory gases and a paramagnetic measurement of oxygen. At Lincoln Medical Center, the gas analyser used will be a Philips G5 gas analyser connected to a Philips Intellivue MP 70. At the University of New Mexico Medical Center, the Masimo root monitor is used.

The gas analysers produce display waves for O2 and CO2, together with numerics for end-tidal values for O2 and CO2 and to our knowledge, there are no differences in values between the various devices used. The gas sampling occurs through a side-stream sampling tube at a rate of 200ml/min ±20 ml/min, which is either obtained from a nasal cannula in the spontaneously breathing patient or a sidestream line if connected to a BVM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of hypoxia
Time Frame: The time when laryngoscope first enters the mouth to 2 minutes after the endotracheal tube [ETT] is confirmed on waveform capnography
The proportion of patients that experience oxygenation desaturation (SpO2 <93%, or >10% from baseline if SpO2 <93% at the end of preoxygenation) during the peri-intubation period
The time when laryngoscope first enters the mouth to 2 minutes after the endotracheal tube [ETT] is confirmed on waveform capnography

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lowest oxygen saturations
Time Frame: The time when laryngoscope first enters the mouth to 2 minutes after the endotracheal tube [ETT] is confirmed on waveform capnography
The lowest oxygen saturation (SpO2) during the peri-intubation period
The time when laryngoscope first enters the mouth to 2 minutes after the endotracheal tube [ETT] is confirmed on waveform capnography

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time from preoxygenation to endotracheal intubation
Time Frame: Preoxygenation start time to endotracheal intubation confirmation
Time from preoxygenation to endotracheal intubation
Preoxygenation start time to endotracheal intubation confirmation
Incidence of severe oxygen desaturation (SpO2 <80%)
Time Frame: Induction of sedative medications and 2 minutes post ETT confirmation
Incidence of severe oxygen desaturation (SpO2 <80%)
Induction of sedative medications and 2 minutes post ETT confirmation
Incidence of very severe oxygen desaturation (SpO2 <70%)
Time Frame: Induction of sedative medications and 2 minutes post ETT confirmation
Incidence of very severe oxygen desaturation (SpO2 <70%)
Induction of sedative medications and 2 minutes post ETT confirmation
Incidence of the number of patients with pre-oxygenation method changes to achieve higher ETO2 in intervention arm
Time Frame: During preoxygenation

Incidence in pre-oxygenation changes in method to deliver higher ETO2:

  • BVM
  • BVM+PEEP
  • HFNP
  • NIV
During preoxygenation
Incidence of the number of patients with pre-oxygenation technique changes to achieve higher ETO2 in intervention arm
Time Frame: During preoxygenation

Incidence in pre-oxygenation changes in technique to deliver higher ETO2:

  • Improved mask seal
  • Increased O2 flow rate
  • Increased Preoxygenation time
During preoxygenation
Number of re-oxygenation events
Time Frame: During preoxygenation
A re-oxygenation attempt is a failed first attempt at ETT placement followed by administration of an oxygen delivery device (BVM, NIV, supraglottic device) to maintain SpO2 levels
During preoxygenation
Cardiovascular complications during RSI
Time Frame: Induction of sedative medications and 2 minutes post ETT confirmation
  • Bradycardia (HR< 40 bpm)
  • Tachycardia (HR> 120 bpm)
  • Hypotension (SBP< 90 mm Hg or a 30mmHg reduction from baseline)
Induction of sedative medications and 2 minutes post ETT confirmation
Other complications during RSI
Time Frame: Induction of sedative medications and 2 minutes post ETT confirmation
Operator reported aspiration between induction and intubation Oesophageal intubation recognised after the laryngoscope blade has been removed, detected by waveform ETCO2 Cardiac arrest occurred during RSI
Induction of sedative medications and 2 minutes post ETT confirmation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sydney Local Health District

Investigators

  • Study Chair: Matthew Oliver, MBBS, Sydney Local Health District
  • Study Chair: Nick Caputo, Md, Lincoln Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

August 21, 2024

First Submitted That Met QC Criteria

August 27, 2024

First Posted (Actual)

August 29, 2024

Study Record Updates

Last Update Posted (Actual)

August 29, 2024

Last Update Submitted That Met QC Criteria

August 27, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-008

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Following publication, individual patient data will be made available for sharing to researchers with 1) a signed data access agreement, 2) research testing a hypothesis, 3) a protocol that has been approved by an institutional review board, and 4) a proposal that has received approval from the principal investigator.

IPD Sharing Time Frame

No end date

IPD Sharing Access Criteria

a signed data access agreement research testing a hypothesis a protocol that has been approved by an institutional review board a proposal that has received approval from the principal investigator

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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