JOURNAL CLUB – February 2025

JOURNAL CLUB PODCAST FEBRUARY 2025

DR CONOR O’FLYNN

Senior Registrar in Research, The Alfred Emergency & Trauma Centre

DR CRISTINA ROMAN

Lead Pharmacist for Emergency Medicine, The Alfred Emergency & Trauma Centre

PROFESSOR PETER CAMERON

Academic Director, The Alfred Emergency & Trauma Centre

This month, I was joined by Dr Cristina Roman along with Alfred Health Journal Club Podcast stalwart - Professor Peter Cameron to discuss two important trials that address oxygen therapy in critical care settings - TRAUMOX2 and RENOVATE.

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Early Restrictive vs Liberal Oxygen for Trauma Patients: The TRAUMOX2 Randomized Clinical Trial

Read it here: JAMA Article – Early Restrictive vs Liberal Oxygen for Trauma Patients 

Clinical Question

Does an early, 8‑hour restrictive oxygen strategy (targeting an SpO₂ of 94%) reduce death and/or major respiratory complications compared with a liberal oxygen approach in adult trauma patients?

Study Design

Design	Multicenter, open‑label, pragmatic randomized controlled trial
Population	Adult trauma patients (≥18 years) requiring full trauma team activation in various hospitals across Denmark, the Netherlands, and Switzerland
Intervention	A restrictive oxygen strategy initiated in the prehospital setting or on trauma centre admission, titrated to an SpO₂ of 94%
Comparison	A liberal oxygen strategy following ATLS guidelines
Outcome	Primary composite outcome of death and/or major respiratory complications within 30 days; secondary outcomes included rates of atelectasis and opioid requirements, among others.

Findings

The trial enrolled nearly 2,000 patients, with the primary composite outcome occurring in 16.1% versus 16.7% in the restrictive and liberal groups respectively—demonstrating no statistically significant difference. Notably, there was a lower incidence of atelectasis in the restrictive oxygen arm.

Authors' Conclusion

“In adult trauma patients, an early restrictive oxygen strategy did not significantly reduce death and/or major respiratory complications compared with a liberal oxygen strategy. However, the lower rate of atelectasis in the restrictive arm suggests that a more tailored approach to oxygen therapy might benefit specific patient subsets.”

Thoughts from Journal Club:

• This cohort of patients was not on the sicker end of the trauma spectrum, with a mean ISS < 16. Any findings extrapolated to truly sick polytrauma patients requiring product-centric resuscitation should be done tentatively, at best.

• There is a significant risk of contamination bias, with some of the patients having 50 minutes of the contralateral arm before randomisation for an 8-hour treatment period

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High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial

Read it here: JAMA Article – High-Flow Nasal Oxygen vs Noninvasive Ventilation 

Clinical Question

Is high-flow nasal oxygen (HFNO) non-inferior to noninvasive ventilation (NIV) in reducing the composite outcome of endotracheal intubation or death within 7 days in adult patients with acute respiratory failure?

Study Design

Design	Multicenter, adaptive, noninferiority randomized clinical trial conducted at 33 hospitals in Brazil
Population	Hospitalized adults with acute respiratory failure across five groups—including nonimmunocompromised and immunocompromised patients with hypoxemia, patients with COPD exacerbation with respiratory acidosis, acute cardiogenic pulmonary edema, and hypoxemic COVID‑19
Intervention	High-flow nasal oxygen delivered at variable flow rates (titrated up to 60 L/min)
Comparison	NIV delivered via face mask with preset pressure support and PEEP
Outcome	The primary endpoint was the composite of endotracheal intubation or death within 7 days; secondary endpoints included 28‑ and 90‑day mortality, ventilation‑free days, and patient comfort scores.

Findings

Among 1,800 enrolled patients, HFNO met the criteria for noninferiority compared with NIV in four of the five patient groups. In the immunocompromised group, results were inconclusive (stopped for futility), and a post hoc analysis revealed some sensitivity to the chosen statistical model. Importantly, HFNO was associated with superior patient comfort.

Authors' Conclusion

“High-flow nasal oxygen is non-inferior to noninvasive ventilation for the composite outcome of intubation or death within 7 days in most patient groups with acute respiratory failure, supporting its use as an effective and more comfortable alternative in this setting.”

Thoughts from Journal Club

• Robustness of the findings in the COPD group is undermined by the decision to use NIV as the rescue for HFNO, inferring that it is already viewed as a better treatment.

• The results presented differed drastically when dynamic borrowing was in play versus not, which once again challenges the validity of the results, and subsequent interpretation given by the authors.

• The parameters for the borrowing model, which define whether data is similar enough to borrow, are not readily available and this lack of transparency coupled with the significant change in the results when borrowing is applied raises serious questions about internal validity.

• Protocol adherence throughout was poor, barely any of the NIV category received NIV as per the protocol.

• Contamination bias was once again at play with a significant proportion of the patients receiving both arms of the trial.

Dr Conor O'Flynn

Emergency Registrar

Conor is a temporary, so he continually attests, NHS refugee, who joined Alfred Health in 2023. In the emergency department, he can usually be found lurking on the helipad or in the trauma bays, diligently cleaning ultrasounds, or boring medical students about medical history. Outside of work, he is fond of spending his days off over the stove, swimming in the bay or attempting to roll back the years (and ACL reconstructions) on the rugby pitch.