Pain After Cardiac Arrest and Resuscitation (PAINCARE)

Characterizing and Quantifying Pain After Cardiac Arrest and Resuscitation: Insights From the PAINCARE Substudy of the STEPCARE Trial

The PAINCARE substudy is an observational cohort substudy nested within the international STEPCARE trial, which evaluates sedation, temperature, and mean arterial pressure strategies after out-of-hospital cardiac arrest. PAINCARE aims to describe the burden of pain during early intensive care after cardiac arrest and to evaluate associations between early pain burden and selected ICU and patient-reported outcomes. Pain is common in critically ill patients but may be difficult to assess in patients who are unconscious, sedated, mechanically ventilated, or unable to self-report. PAINCARE collects structured pain assessments during the first 168 hours after randomization using validated self-report or behavioral pain instruments and relates early pain burden to outcomes including delirium burden, ventilator-free time, ICU-free time, and follow-up pain outcomes. All analyses are observational; PAINCARE is not designed to determine whether modifying pain burden improves outcomes.

PAINCARE is an exploratory observational substudy. The available sample size is expected to be approximately 300 participants and will be determined by PAINCARE participation, consent status, availability of PAINCARE data, and eligibility for the relevant analysis population. The primary analysis will estimate cumulative time in moderate/severe pain while alive and in the ICU from randomization through 168 hours, ICU discharge, or death, whichever occurs first. Secondary analyses will evaluate associations between early pain burden and selected ICU and patient-reported outcomes. Missingness will be reported by variable, timepoint, site, and ascertainment mode where feasible. Prespecified analysis rules distinguish missing scorable intervals from non-scorable intervals, allow deterministic imputation only for isolated missing scorable intervals meeting prespecified criteria, and use endpoint-specific analysis populations for secondary and exploratory analyses. Sensitivity analyses will assess robustness to assumptions about pain-data completeness, deterministic imputation, non-scorable intervals, pain-state thresholds, and ascertainment mode. Analyses will be primarily descriptive and associational; findings outside the primary analysis will be considered hypothesis-generating. PAINCARE includes both retrospectively and prospectively ascertained participants according to local approvals and substudy implementation.

Inclusion Criteria:

• Out-of-hospital cardiac arrest
• Adult, age 18 years or older
• Spontaneous circulation without chest compressions for at least 20 minutes
• Comatose, defined as not obeying verbal commands
• Enrolled within 4 hours after return of spontaneous circulation

Exclusion Criteria:

• Restrictions or limitations of care
• On extracorporeal membrane oxygenation before randomization
• Pregnancy
• Previously randomized in the STEPCARE trial
• Trauma or hemorrhage as the presumed cause of arrest
• Suspected or confirmed intracranial hemorrhage