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<p>The benefits of non-invasive respiratory support strategies (NIRS), such as high-flow nasal oxygen therapy, in delaying intubation remain uncertain. We used an emulated target trial approach to evaluate outcomes associated with late intubation in patients with severe acute respiratory failure due to COVID-19. We conducted a retrospective multicentre cohort study using the French prospective OUTCOMEREA database. Adult patients admitted to intensive care units (ICUs) for severe SARS-CoV-2 pneumonia with an ICU length of stay of at least seven days were included in the study. Descriptive analyses were used to compare patients who were intubated after day 6 with those who remained under NIRS. In the emulated target trial, patients who were eligible between ICU days 7 and 12 were assigned to undergo late intubation or to remain under NIRS. Weighted Cox proportional hazards models were used. The primary outcome was 60-day mortality. Of the 1206 ICU patients with SARS-CoV-2 pneumonia, 288 were still in the ICU on day 7. Of these, 65 (22.6%) subsequently underwent late intubation and had a 60-day mortality rate of 78.5%. In the emulated target trial, which included 234 patients at risk of intubation, 57 underwent late intubation. Late intubation was associated with a higher risk of death (adjusted hazard ratio: 2.89; 95% confidence interval: 1.50–3.92). The estimated absolute difference in 60-day survival was − 0.34 (95% CI − 0.62 to 0.30). The restricted mean survival time was 17.8&#xa0;days shorter in the late intubation group (95% CI − 30.6 to 10.8). In this multicentre cohort, patients requiring late intubation had a very high mortality rate. In the emulated target trial analysis, late intubation was associated with poorer survival compared to continued NIRS, suggesting a subgroup of patients with progressive respiratory failure rather than a direct effect of intubation timing.</p>

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Delayed intubation and 60-day mortality in severe COVID-19-associated acute respiratory failure in an emulated target trial using the OUTCOMEREA network

  • 期刊论文

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  • 发表日期：

    2026年6月23日

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  • Mathilde Phillips-Houlbracq,
  • Mathilde Neuville,
  • Karl Bitar,
  • Shidasp Siami,
  • Yves Cohen,
  • Virginie Laurent,
  • Bruno Mourvillier,
  • Jean Reignier,
  • Dany Goldgran-Toledano,
  • Carole Schwebel,
  • Stéphane Ruckly,
  • Etienne de Montmollin,
  • Niccolo Buetti,
  • Charles Cerf,
  • Jean-François Timsit,
  • Claire Dupuis,
  • Jean-François Timsit,
  • Elie Azoulay,
  • Maïté Garrouste-Orgeas,
  • Jean-Ralph Zahar,
  • Bruno Mourvillier,
  • Michael Darmon,
  • Niccolo Buetti,
  • Jean-Francois Timsit,
  • Corinne Alberti,
  • Stephane Ruckly,
  • Sébastien Bailly,
  • Aurélien Vannieuwenhuyze,
  • Christophe Adrie,
  • Carole Agasse,
  • Bernard Allaouchiche,
  • Olivier Andremont,
  • Pascal Andreu,
  • Laurent Argaud,
  • Elie Azoulay,
  • Francois Barbier,
  • Jean-Pierre Bedos,
  • Jérome Bedel,
  • Asael Berger,
  • Julien Bohé,
  • Lila Bouadma,
  • Jeremy Bourenne,
  • Noel Brule,
  • Frank Chemouni,
  • Julien Carvelli,
  • Martin Cour,
  • Michael Darmon,
  • Anais Dartevelle,
  • Julien Dessajan,
  • Claire Dupuis,
  • Etienne de Montmollin,
  • Marc Doman,
  • Loa Dopeux,
  • Anne-Sylvie Dumenil,
  • Claire Dupuis,
  • Jean-Marc Forel,
  • Marc Gainnier,
  • Charlotte Garret,
  • Louis-Marie Galerneau,
  • Dany Goldgran-Tonedano,
  • Steven Grangé,
  • Antoine Gros,
  • Hédia Hammed,
  • Akim Haouache,
  • Tarik Hissem,
  • Vivien Hong Tuan Ha,
  • Sébastien Jochmans,
  • Jean-Baptiste Joffredo,
  • Hatem Kallel,
  • Guillaume Lacave,
  • Virgine Laurent,
  • Alexandre Lautrette,
  • Clément Le Bihan,
  • Virgine Lemiale,
  • David Luis,
  • Jordane Lebut,
  • Bruno Mourvillier,
  • Benoît Misset,
  • Bruno Mourvillier,
  • Mathild Neuville,
  • Laurent Nicolet,
  • Johanna Oziel,
  • Laurent Papazian,
  • Juliette Patrier,
  • Benjamin Planquette,
  • Aguila Radjou,
  • Romain Sonneville,
  • Jean Reignier,
  • Bertrand Souweine,
  • Carole Schwebel,
  • Shidasp Siami,
  • Romain Sonneville,
  • Michael Thy,
  • Gilles Troché,
  • Fabrice Thiollieres,
  • Guillaume Thierry,
  • Michael Thy,
  • Guillaume Van Der Meersch,
  • Marion Venot,
  • Florent Wallet,
  • Sondes Yaacoubi,
  • Olivier Zambon,
  • Jonathan Zarka,
  • Kévin Grapin,
  • Francois Thouy,
  • Laure Calvet,
  • Kevin Grapin,
  • Guillaume Laurichesse,
  • Neven Stevic,
  • Mireille Adda,
  • Clémence Barberot,
  • Vanessa Vindrieux,
  • Marion Provent,
  • Pauline Enguerrand,
  • Vincent Gobert,
  • Stéphane Guessens,
  • Hélène Merle,
  • Nadira Kaddour,
  • Boris Berthe,
  • Samir Bekkhouche,
  • Kaouttar Mellouk,
  • Mélaine Lebrazic,
  • Carole Ouisse,
  • Diane Maugars,
  • Christelle Aparicio,
  • Igor Theodose,
  • Manal Nouacer,
  • Véronique Deiler,
  • Fariza Nait Sidenas,
  • Myriam Moussa,
  • Atika Mouaci,
  • Nassima Viguier

摘要

The benefits of non-invasive respiratory support strategies (NIRS), such as high-flow nasal oxygen therapy, in delaying intubation remain uncertain. We used an emulated target trial approach to evaluate outcomes associated with late intubation in patients with severe acute respiratory failure due to COVID-19. We conducted a retrospective multicentre cohort study using the French prospective OUTCOMEREA database. Adult patients admitted to intensive care units (ICUs) for severe SARS-CoV-2 pneumonia with an ICU length of stay of at least seven days were included in the study. Descriptive analyses were used to compare patients who were intubated after day 6 with those who remained under NIRS. In the emulated target trial, patients who were eligible between ICU days 7 and 12 were assigned to undergo late intubation or to remain under NIRS. Weighted Cox proportional hazards models were used. The primary outcome was 60-day mortality. Of the 1206 ICU patients with SARS-CoV-2 pneumonia, 288 were still in the ICU on day 7. Of these, 65 (22.6%) subsequently underwent late intubation and had a 60-day mortality rate of 78.5%. In the emulated target trial, which included 234 patients at risk of intubation, 57 underwent late intubation. Late intubation was associated with a higher risk of death (adjusted hazard ratio: 2.89; 95% confidence interval: 1.50–3.92). The estimated absolute difference in 60-day survival was − 0.34 (95% CI − 0.62 to 0.30). The restricted mean survival time was 17.8 days shorter in the late intubation group (95% CI − 30.6 to 10.8). In this multicentre cohort, patients requiring late intubation had a very high mortality rate. In the emulated target trial analysis, late intubation was associated with poorer survival compared to continued NIRS, suggesting a subgroup of patients with progressive respiratory failure rather than a direct effect of intubation timing.