According to the WEAN‑SAFE trial in The Lancet, how should a stable adult ICU patient receiving long‑term opioids, benzodiazepines, systemic steroids, and invasive mechanical ventilation be weaned safely?

Safe Weaning from Mechanical Ventilation: Evidence from the WEAN SAFE Trial

Based on the WEAN SAFE trial published in The Lancet Respiratory Medicine, only 65% of critically ill patients receiving mechanical ventilation for ≥2 days were successfully weaned at 90 days, with delayed weaning initiation and excessive sedation being the primary modifiable factors associated with weaning failure. 1

Key Findings from WEAN SAFE That Should Guide Clinical Practice

Epidemiology and Outcomes

• Among 5,869 patients ventilated ≥2 days across 481 ICUs in 50 countries, 77.1% underwent at least one separation attempt, but only 65% achieved successful weaning by day 90 1
• 28.3% of patients died while still invasively ventilated, and overall hospital mortality reached 38.3% 1
• Weaning duration breakdown: 64.7% had short weaning (≤1 day), 10.1% intermediate (2-6 days), 9.6% prolonged (≥7 days), and 15.6% experienced weaning failure 1

Critical Modifiable Risk Factors Identified

Sedation Management:

• Higher sedation scores were independently associated with both delayed weaning initiation AND weaning failure 1
• Minimize continuous or intermittent sedation in mechanically ventilated patients, targeting specific titration endpoints 2
• Use protocol-driven sedation minimization strategies, as limiting sedation reduces mechanical ventilation duration and ICU length of stay 2

Timing of Weaning Initiation:

• Median time from meeting weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4 days) 1
• However, 22.4% of patients experienced delays of ≥5 days in initiating first separation attempt 1
• Delayed initiation of weaning was independently associated with weaning failure 1

Recommended Weaning Protocol Based on Current Evidence

Step 1: Daily Readiness Screening

Perform daily assessment using these criteria before attempting spontaneous breathing trial (SBT): 2, 3, 4

• FiO₂ <0.50 with SpO₂ >90%
• PEEP ≤5 cm H₂O
• Respiratory rate <30 breaths/minute
• Hemodynamically stable (no active myocardial ischemia, minimal vasopressor requirements)
• Patient arousable with adequate mental status
• Intact airway reflexes
• No new potentially serious conditions

Step 2: Conduct Spontaneous Breathing Trial

Use 30 minutes of pressure support ventilation (5-8 cm H₂O) rather than T-piece or longer duration trials: 3, 4, 5

• This approach achieves 82.3% successful extubation vs 74.0% with 2-hour T-piece trials (8.2% absolute difference, P=0.001) 5
• SBT success rate is 84.6% with pressure support vs 76.7% with T-piece (RR 1.11,95% CI 1.02-1.18) 3, 4
• Most SBT failures occur within the first 30 minutes 4

Terminate SBT immediately if any of these develop: 3, 4

• Respiratory distress (increased respiratory rate, accessory muscle use, paradoxical breathing)
• Hemodynamic instability (tachycardia, hypertension, hypotension)
• Oxygen desaturation or deteriorating gas exchange
• Altered mental status or agitation
• Diaphoresis or subjective discomfort

Step 3: Pre-Extubation Assessment

Before extubating, evaluate: 4, 6

• Upper airway patency (perform cuff leak test if risk factors present: prolonged intubation, difficult/traumatic intubation, large ETT, high cuff pressures)
• Bulbar function and swallowing capability
• Cough effectiveness
• Sputum load and secretion management ability

Step 4: Post-Extubation Management

For high-risk patients (prolonged ventilation >14 days, chronic lung disease, myocardial dysfunction, neurologic impairment, previously failed extubation): 6

• Consider prophylactic noninvasive ventilation (NIV) immediately after extubation
• Ensure physiotherapist presence during extubation to manage immediate complications
• Use high-flow oxygen therapy for hypoxemic patients at lower risk

Critical Pitfalls to Avoid Based on WEAN SAFE Data

Do NOT Repeat SBTs on Same Day After Failure

• Failed SBTs indicate respiratory muscle fatigue; forcing repeat attempts worsens outcomes 4
• After SBT failure, identify and address underlying causes before next attempt (typically next day) 4
• Failed extubation requiring reintubation increases mortality by 10-20% 6

Do NOT Use Gradual Weaning Methods

• Use daily SBTs with ventilator liberation protocols rather than SIMV or progressive PSV reduction 2, 3
• Protocol-driven SBT approach reduces mechanical ventilation duration by approximately 50% and achieves extubation three times faster than gradual methods 3
• This represents a conditional recommendation with moderate certainty evidence from the ATS/CHEST guidelines 2

Do NOT Delay Weaning Initiation

• The WEAN SAFE trial identified that 22.4% of patients had unnecessary delays ≥5 days in starting separation attempts 1
• Median time should be 1 day from meeting eligibility criteria to first separation attempt 1
• Delays are independently associated with weaning failure 1

Medication Weaning Considerations

Sedation Weaning

The WEAN SAFE trial specifically identified excessive sedation as an independent predictor of weaning failure 1

• Implement nurse-directed sedation protocols incorporating sedation scales 2
• Consider intermittent rather than continuous sedation 2
• Prioritize short-acting agents (propofol, dexmedetomidine) over benzodiazepines 2

Opioid and Benzodiazepine Management

• While the WEAN SAFE trial did not specifically address opioid/benzodiazepine tapering protocols, the strong association between sedation levels and weaning failure indicates these should be minimized during weaning attempts 1
• Use opioids alone when possible, avoiding sedatives, which allows more rapid liberation from mechanical ventilation 2

Systemic Steroid Considerations

• The evidence provided does not address steroid weaning during mechanical ventilation liberation
• However, prophylactic corticosteroids (prednisolone 1 mg/kg/day) may be considered for patients with low cuff leak volume before extubation, initiated at least 6 hours prior 2

Target Acceptable Extubation Failure Rate

• Maintain extubation failure rate between 5-10% 4
• Higher rates suggest inadequate readiness assessment; lower rates suggest overly conservative approach delaying liberation 4
• Approximately 10% of patients who pass SBT will still fail extubation within 48 hours 4, 6