Weaning Delays and Sedation Levels Affect Outcomes of Patients With IMV

When weaning critically ill patients from invasive mechanical ventilation (IMV), success rates and patient survival may be improved by reducing delays in weaning initiation and optimizing sedation levels during weaning, according to study findings published in The Lancet Respiratory Medicine.

High failure rates and poor outcomes from weaning critically ill patients from invasive mechanical ventilation (IMV) are typical. The Worldwide Assessment of Separation of Patients from Ventilatory Assistance (WEAN SAFE; ClinicalTrials.gov Identifier: NCT03255109), a prospective study done in 481 intensive care units (ICUs) in 50 countries, sought to understand the weaning process in a large, real-world population.

The primary endpoint for the trial was the proportion of patients at 90 days who were successfully weaned. Secondary endpoints included timing of weaning events, factors associated with weaning delay and weaning failure, weaning duration, and hospital outcomes. The investigators hypothesized that variations and gaps in the weaning process were associated with delayed and failed weaning.

Conducted from October 2017 through June 2018, WEAN SAFE involved 5869 critically ill patients over the age of 16 years (median age, 64 years; interquartile range, 51-74) receiving mechanical ventilation for at least 2 calendar days. Of those patients, 38.2% were women and 65.5% had at least 1 relevant comorbidity, most commonly diabetes (21.5%), smoking (14.5%), and chronic obstructive pulmonary disease (13.6%).

Weaning initiation was defined as the first attempt to separate patient from ventilator. Successful weaning meant no reintubation or death within 7 days of extubation. Weaning criteria were based on fractional concentration of oxygen in inspired air (<0.5), positive end-expiratory pressure (<10 cm H₂O), and no or low doses of vasopressors (<0.2 µg/kg per minute of norepinephrine or equivalent).

Of the patients analyzed:

• 91.5% met weaning eligibility criteria at a median of 3 days following tracheal intubation;
• 92.6% presented signs of spontaneous breathing activity at a median of 3 days following tracheal intubation;
• 77.1% underwent at least 1 separation attempt; and
• 65.0% were successfully weaned from ventilation at day 90.

Researchers noted the median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (interquartile range, 0-4) and 22.4% of patients had a delay in initiating first separation of at least 5 days. There were 4.0% of patients transferred before any separation attempt, 2.6% who were transferred after at least 1 attempt and not successfully weaned, and 28.3% who died while invasively ventilated.

Among the patients with separation attempts, 64.7% had a short wean (≤1 day), 10.1% had an intermediate wean (2-6 days), 9.6% had a prolonged wean (≥7 days), and 15.6% experienced weaning failure.

Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure.

Among the study population, there were 1742/5479 deaths (31.8%) in the intensive care unit and 2095/5465 deaths (38.3%) in-hospital. Of the ICU deaths, 1109/1742 occurred before any separation attempt, 553 occurred in patients who had an unsuccessful separation attempt, and 80 occurred in patients who had been weaned from IMV.

Study limitations include interpretation of radiographs and other source data by on-site clinicians, which may have increased variability; failure to distinguish between weaning and extubation; selection bias; the assumption that patients discharged before day 90 were still alive at day 90; and the fact that a small proportion of patients were lost to follow-up.

Overall, 65% of patients requiring invasive ventilation for at least 2 days were successfully weaned from invasive ventilation at day 90, said the study authors. They further noted that the study found “Potentially important practice variations across patients…in the weaning process.” They added that “Optimizing sedation levels during weaning was identified as a key potentially modifiable variable to enhance weaning success rates.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.