Acute hypoxemic respiratory failure requires endotracheal intubation and invasive mechanical ventilation in approximately 30-40% of cases, due to severe hypoxemia and/or clinical signs of acute respiratory distress. The primary objectives of invasive mechanical ventilation are to reduce respiratory effort and improve oxygenation. However, this intervention is also associated with both direct and indirect adverse effects, mainly linked to the need for sedation and often neuromuscular blockade. These include hemodynamic compromise, neuromuscular weakness, ventilator-induced lung injury, and infectious complications.
An ideal intubation strategy would therefore strike a balance: avoiding the risks of delayed intubation-such as refractory hypoxemia, excessive respiratory effort, and patient self-inflicted lung injury (P-SILI)-while limiting complications associated with invasive mechanical ventilation by withholding it in patients who might otherwise recover without. To date, the optimal strategy for achieving this risk-benefit balance remains uncertain.
Clinical practice suggests a broad consensus on the necessity of intubation when so-called safety criteria are met: severe hypoxemia (SaO₂/FiO₂ ratio \< 88), marked respiratory distress (use of accessory muscles, thoracoabdominal paradox, respiratory rate \> 40/min), extra-respiratory manifestations of hypoxia (e.g., altered consciousness), and/or uncontrolled hemodynamic instability. Beyond these safety thresholds, however, debate persists. Some advocate for earlier intubation-a so-called liberal approach-triggered by predefined hypoxemia criteria (e.g., SpO₂/FiO₂ \< 110), with the aim of limiting the deleterious consequences of sustained hypoxemia.
In routine practice, the criteria guiding intubation vary widely between clinicians and cannot be attributed to strong scientific evidence. This study therefore seeks to compare, in a randomized interventional design, the two main strategies currently applied across centers:
* Liberal intubation strategy: prioritizing the prevention of organ dysfunction related to hypoxemia (notably hypoxic cardiac arrest) and the risk of P-SILI. * Restrictive intubation strategy: prioritizing the reduction of invasive mechanical ventilation use, with the goal of minimizing ventilation-related harm and its associated therapeutic burden.
Adult patient
Patient admitted to intensive care less than 24 hours ago
Oxygen therapy ≥ 10 L/min via high-concentration mask required for 92 ≤ SpO2 ≤ 98%
High-flow oxygen therapy with FiO2 ≥ 50% required for 92 ≤ SpO2 ≤ 98%
Acute hypercapnic respiratory failure (defined by PaCO2 > 45 mmHg)
Cardiogenic pulmonary edema
Exacerbation of chronic respiratory disease
Respiratory failure requiring long-term oxygen therapy
Parallel
Restrictive intubation strategy
Procedure/SurgeryEndotracheal intubation is recommended only if at least one of the following criteria persists for more than 5 minutes: 1. Respiratory rate \> 40/min, persistent use of accessory muscles, or thoracoabdominal paradox. 2. SpO₂/FiO₂ \< 88. 3. Neurological or systemic impairment attributable to hypoxemia, defined as: altered higher brain functions without another identifiable cause, Glasgow Coma Scale ≤ 12, uncontrolled hemodynamic instability, or rising lactate levels.
Liberal intubation strategy
Procedure/SurgeryEndotracheal intubation is recommended if SpO₂/FiO₂ \< 110 for more than 5 minutes. In addition, intubation is also recommended in the liberal strategy if any of the restrictive strategy criteria occur and persist for more than 5 minutes.
Impact of a liberal intubation strategy compared to a restrictive strategy in regards to organ support duration, taking mortality into account
Composite endpoint consisting of death and number of days with organ failure at D28, analyzed using the Win Ratio method.
Evaluate the impact of the intubation strategy on intubation rates over time.
Time of intubation (if performed).
Assess the impact of the intubation strategy on each component of the composite primary endpoint.
Components of the composite primary endpoint: * All-cause mortality * Duration of mechanical ventilation * Duration of vasopressor support * Duration of renal replacement therapy
Assess the impact of the intubation strategy on the severity of vital organ failure and the duration of care.
Measurements of SOFA score (points), Length of stay in the intensive care unit (days) and total hospital length of stay (days) SOFA is Sepsis-related Organ Failure Assessment : score range form 0 to 24, the higher scores indicating the the more severe condition
Assess the impact of the intubation strategy on quality of life at day 90.
5Level-EuroQuol-5Dimensions score (EQ-5D-5L). The scale measures quality of life on a 5-component scale. A health state of 11,111 indicate no problem in any dimension, a health state of 55,555 indicates extreme problems in every dimension
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