Single-cell transcriptomes of zebrafish germline reveal progenitor types and feminization by Foxl2l.

BACKGROUND

Over 1 in 5 Americans die in intensive care units (ICUs), among whom 50% undergo palliative withdrawal of mechanical ventilation (WMV). Little is known about their experience or best practices to minimize their suffering.

RESEARCH QUESTION: To describe and identify factors associated with patient distress post-WMV.

STUDY DESIGN AND

METHODS

Observational study of Withdrawal of Mechanical Ventilation (OBSERVE-WMV) is a prospective cohort study conducted from January 2021 to July 2022 in 12-ICUs at two academic medical centers among mechanically ventilated intubated patients transitioning to comfort-focused care via WMV. The cumulative incidence of experiencing distressful episodes from either observed respiratory distress (Respiratory distress observation score >3 or self-reported dyspnea rated ≥5), Pain (Visual Analog Scale or Clinical Pain Observation Tool ≥3), or agitation (Richmond Agitation Sedation Scale ≥+2) from the time of WMV initiation until death (or up to 3-hours post-WMV) were calculated. Multivariable Poisson Regression identified factors associated with the number of distressful episodes, adjusting for time at risk, generating adjusted incidence risk ratios (aIRRs) with 95% confidence intervals (CIs).

RESULTS

Among 153 participants, the cumulative incidence of at least one distressful episode post-WMV was 91% (individual symptoms were: respiratory distress, 90%; pain, 56%; and agitation, 5%), with 41% of patients having > 3 episodes. In multivariable analysis, receiving opiates within 1-hour before WMV (anticipatory dosing) was associated with lower risk of distressful episodes (aIRR 0.74, CI 0.55-0.99). Factors associated with higher risk of distressful episodes included: ICU stays > 10 days (aIRR 1.85, CI 1.20-2.88), lower levels of consciousness (lower Glasgow Coma Scale) (aIRR 1.72, CI 1.06-2.78), and distressful episodes pre-WMV (aIRR 1.63, CI 1.21-2.18).

INTERPRETATION: Nearly all ICU patients undergoing palliative WMV at end-of-life demonstrated distressful symptoms or signs. Anticipatory dosing with opiates prior to WMV may help mitigate their distress.