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[Preprint]. 2023 Mar 24:2023.03.23.23287539.

doi: 10.1101/2023.03.23.23287539.

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask

Kevin W Gibbs¹, Adit A Ginde², Matthew E Prekker^{3

4}, Kevin P Seitz⁵, Susan B Stempek⁶, Caleb Taylor⁷, Sheetal Gandotra⁸, Heath White⁹, Daniel Resnick-Ault², Akram Khan¹⁰, Amira Mohmed¹¹, Jason C Brainard¹², Daniel G Fein¹³, Neil R Aggarwal¹⁴, Micah R Whitson^{8

15}, Stephen J Halliday¹⁶, John P Gaillard^{17

18}, Veronika Blinder¹¹, Brian E Driver⁴, Jessica A Palakshappa¹, Bradley D Lloyd¹⁹, Joanne M Wozniak⁶, Matthew C Exline⁷, Derek W Russell^{8

20}, Shekhar Ghamande⁹, Cori Withers², Kinsley A Hubel¹⁰, Ari Moskowitz¹¹, Jill Bastman², Luke Andrea¹¹, Peter D Sottile¹⁴, David B Page⁸, Micah T Long²¹, Jordan Kugler Goranson¹⁸, Rishi Malhotra¹¹, Brit J Long²², Steven G Schauer²³, Andrew Connor¹⁰, Erin Anderson², Kristin Maestas², Jillian P Rhoads⁵, Kelsey Womack⁵, Brant Imhoff²⁴, David R Janz²⁵, Stacy A Trent^{2

26}, Wesley H Self¹⁹, Todd W Rice⁵, Matthew W Semler⁵, Jonathan D Casey⁵

Affiliations

¹ Section on Pulmonary, Critical Care, Allergy, and immunology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
² Department of Emergency Medicine, University of Colorado School of Medicine Aurora, CO, USA.
³ Division of Pulmonary and Critical Care Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
⁴ Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
⁵ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Medicine, Division of Pulmonary & Critical Care Medicine, Lahey Hospital & Medical Center, Burlington, MA, USA.
⁷ Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, USA.
⁸ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Department of Medicine, Division of pulmonary & Critical Care Medicine, Baylor Scott & White Medical Center, Temple, TX, USA.
¹⁰ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA.
¹¹ Division of Critical Care Medicine Montefiore Medical Center Bronx, NY, USA.
¹² Department of Anesthesiology University of Colorado School of Medicine Aurora, CO, USA.
¹³ Division of Pulmonary Medicine Montefiore Medical Center Bronx, NY, USA.
¹⁴ Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁵ Department of Emergency Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wi, USA.
¹⁷ Department of Anesthesiology, Section on Critical Care ,Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁸ Department of Emergency Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁹ Vanderbilt Institute for Clinical and Translational Research, and Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁰ Pulmonary Section, Birmingham VA medical Center, Birmingham, AL, USA.
²¹ Department of Anesthesiology, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
²² 59 Medical Wing, United States Air Force, Fort Sam Houston, San Antonio, TX, USA.
²³ United States Army Institute of Surgical Research, Joint Base San Antonio-Fort Sam Houston, San Antoni, TX, USA.
²⁴ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁵ University Medical Center New Orleans and the Department of Medicine, Section of Pulmonary/Critical Care Medicine and Allergy/Immunology, Louisiana State University School of Medicine, New Orleans, LA, USA.
²⁶ Department of Emergency Medicine, Denver Health Medical Center, Denver, CO, USA.

PMID: 36993496
PMCID: PMC10055579
DOI: 10.1101/2023.03.23.23287539

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask

Kevin W Gibbs et al. medRxiv. 2023.

[Preprint]. 2023 Mar 24:2023.03.23.23287539.

doi: 10.1101/2023.03.23.23287539.

Authors

Affiliations

¹ Section on Pulmonary, Critical Care, Allergy, and immunology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
² Department of Emergency Medicine, University of Colorado School of Medicine Aurora, CO, USA.
³ Division of Pulmonary and Critical Care Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
⁴ Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
⁵ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Medicine, Division of Pulmonary & Critical Care Medicine, Lahey Hospital & Medical Center, Burlington, MA, USA.
⁷ Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, USA.
⁸ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Department of Medicine, Division of pulmonary & Critical Care Medicine, Baylor Scott & White Medical Center, Temple, TX, USA.
¹⁰ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA.
¹¹ Division of Critical Care Medicine Montefiore Medical Center Bronx, NY, USA.
¹² Department of Anesthesiology University of Colorado School of Medicine Aurora, CO, USA.
¹³ Division of Pulmonary Medicine Montefiore Medical Center Bronx, NY, USA.
¹⁴ Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁵ Department of Emergency Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁶ Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wi, USA.
¹⁷ Department of Anesthesiology, Section on Critical Care ,Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁸ Department of Emergency Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁹ Vanderbilt Institute for Clinical and Translational Research, and Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁰ Pulmonary Section, Birmingham VA medical Center, Birmingham, AL, USA.
²¹ Department of Anesthesiology, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
²² 59 Medical Wing, United States Air Force, Fort Sam Houston, San Antonio, TX, USA.
²³ United States Army Institute of Surgical Research, Joint Base San Antonio-Fort Sam Houston, San Antoni, TX, USA.
²⁴ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁵ University Medical Center New Orleans and the Department of Medicine, Section of Pulmonary/Critical Care Medicine and Allergy/Immunology, Louisiana State University School of Medicine, New Orleans, LA, USA.
²⁶ Department of Emergency Medicine, Denver Health Medical Center, Denver, CO, USA.

PMID: 36993496
PMCID: PMC10055579
DOI: 10.1101/2023.03.23.23287539

Abstract

Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure ("preoxygenation") decreases the risk of hypoxemia during intubation.

Research question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain.

Study design and methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023.

Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial.

Clinical trial registration number: NCT05267652.

Keywords: Endotracheal intubation; critical illness; non-invasive positive pressure ventilation; oxygen; respiratory failure.

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Conflict of interest statement

Conflicts of Interest and Financial Disclosures: Kevin W. Gibbs MD reports financial support and travel were provided by US Department of Defense. Adit. A. Ginde MD MPH reports financial support was provided by US Department of Defense. Matthew E. Prekker MD MPH reports financial support was provided by US Department of Defense. Kevin P. Seitz MD MSc reports financial support was provided by National Heart Lung and Blood Institute. Susan B. Stempek PA MBA reports financial support was provided by American College of Chest Physicians. Akram Khan MD reports financial support was provided by United Therapeutics Corporation. Akram Khan MD reports financial support was provided by 4D Medicine Ltd. Akram Khan MD reports financial support was provided by Regeneron Pharmaceuticals Inc. Akram Khan MD reports financial support was provided by Roche. Akram Khan MD reports financial support was provided by Dompé pharmaceutical. Jessica A. Palakshappa MD MS reports financial support was provided by National Institute on Aging. Joanne M. Wozniak PA MS reports was provided by American College of Chest Physicians. Matthew C. Exline MD, MPH reports financial support was provided by Abbott Laboratories. Derek W. Russell MD reports financial support was provided by National Heart Lung and Blood Institute. Shekar Ghamande MD reports financial support was provided by US Department of Defense. Ari Moskowitz MD MPH reports financial support was provided by National Heart Lung and Blood Institute. Jill Bastman BSN reports financial support was provided by US Department of Defense. Micah T. Long MD reports financial support was provided by pocket cards. Steven G. Schauer DO MS reports was provided by US Department of Defense. David Janz MD MSc reports financial support was provided by US Department of Defense. Matthew W. Semler MD MSc reports financial support was provided by US Department of Defense. Matthew W. Semler MD MSc reports financial support was provided by National Heart Lung and Blood Institute. Jonathan D. Casey MD MSc reports was provided by US Department of Defense. Jonathan D. Casey MD MSc reports was provided by National Heart Lung and Blood Institute. Jonathan D. Casey MD MSc reports travel was provided by Fisher & Paykel Healthcare Inc. Todd W Rice MD MSc reports a relationship with Cumberland Pharmaceuticals Inc that includes: consulting or advisory and equity or stocks. Derek W. Russell MD reports a relationship with Achieve Life Science Inc that includes: equity or stocks. Matthew W. Semler MD MSc reports a relationship with Baxter International Inc that includes: consulting or advisory.

References

1. Russotto V, Myatra SN, Laffey JG, et al. Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries. JAMA. Mar 23 2021;325(12):1164–1172. doi:10.1001/jama.2021.1727 - DOI - PMC - PubMed
1. Casey JD, Janz DR, Russell DW, et al. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med. Feb 28 2019;380(9):811–821. doi:10.1056/NEJMoa1812405 - DOI - PMC - PubMed
1. Davis DP, Dunford JV, Poste JC, et al. The impact of hypoxia and hyperventilation on outcome after paramedic rapid sequence intubation of severely head-injured patients. J Trauma. Jul 2004;57(1):1–8; discussion 8-10. doi:10.1097/01.ta.0000135503.71684.c8 - DOI - PubMed
1. April MD, Arana A, Reynolds JC, et al. Peri-intubation cardiac arrest in the Emergency Department: A National Emergency Airway Registry (NEAR) study. Resuscitation. May 2021;162:403–411. doi:10.1016/j.resuscitation.2021.02.039 - DOI - PubMed
1. Smischney NJ, Khanna AK, Brauer E, et al. Risk Factors for and Outcomes Associated With Peri-Intubation Hypoxemia: A Multicenter Prospective Cohort Study. J Intensive Care Med. Dec 2021;36(12):1466–1474. doi:10.1177/0885066620962445 - DOI - PubMed

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This is a preprint.

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask

Affiliations

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical