Emulating Target Trials Comparing Early and Delayed Intubation Strategies

• Published in: Chest Vol. 164; no. 4; pp. 885 - 891
• Main Authors: Wanis, Kerollos Nashat, Madenci, Arin L., Hao, Sicheng, Moukheiber, Mira, Moukheiber, Lama, Moukheiber, Dana, Moukheiber, Sulaiman, Young, Jessica G., Celi, Leo Anthony
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2023; American College of Chest Physicians
• Subjects: causal inference; Critical Care; Critical Care: Original Research; Critical Illness - therapy; high-flow nasal cannula; Humans; intubation; Intubation, Intratracheal; machine learning; noninvasive ventilation; Noninvasive Ventilation - methods; Respiration, Artificial; target trial; AIPW; MIMIC-IV; noninvasive ventilation; target trial; intubation; causal inference; machine learning; high-flow nasal cannula
• ISSN: 0012-3692; 1931-3543; 1931-3543
• DOI: 10.1016/j.chest.2023.04.048

Whether intubation should be initiated early in the clinical course of critically ill patients remains a matter of debate. Results from prior observational studies are difficult to interpret because of avoidable flaws including immortal time bias, inappropriate eligibility criteria, and unrealistic treatment strategies.
Do treatment strategies that intubate patients early in the critical care admission improve 30-day survival compared with strategies that delay intubation?
We estimated the effect of strategies that require early intubation of critically ill patients compared with those that delay intubation. With data extracted from the Medical Information Mart for Intensive Care-IV database, we emulated three target trials, varying the flexibility of the treatment strategies and the baseline eligibility criteria.
Under unrealistically strict treatment strategies with broad eligibility criteria, the 30-day mortality risk was 7.1 percentage points higher for intubating early compared with delaying intubation (95% CI, 6.2-7.9). Risk differences were 0.4 (95% CI, –0.1 to 0.9) and –0.9 (95% CI, –2.5 to 0.7) percentage points in subsequent target trial emulations that included more realistic treatment strategies and eligibility criteria.
When realistic treatment strategies and eligibility criteria are used, strategies that delay intubation result in similar 30-day mortality risks compared with those that intubate early. Delaying intubation ultimately avoids intubation in most patients.
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