Description

The PAINCARE substudy is an observational component embedded within the international, multicenter STEPCARE trial(NCT05706194), which investigates sedation, analgesia, and outcomes in adult patients resuscitated after cardiac arrest. PAINCARE focuses on the assessment, management, and consequences of pain in this patient population during intensive care unit (ICU) treatment and recovery.

Pain is common among critically ill patients but is often underestimated and undertreated, particularly in those who are sedated or mechanically ventilated. Following cardiac arrest, patients may experience pain caused by chest compressions, defibrillation, invasive procedures, or prolonged immobility. Despite this, systematic knowledge about how pain is assessed and treated in post-cardiac arrest patients is limited. Furthermore, little is known about how pain and analgesic management relate to short-term outcomes such as delirium or ICU stay, or to long-term outcomes such as functional recovery and health-related quality of life.

The main objectives of PAINCARE are to (1) describe pain intensity, pain assessment practices, and analgesic use among post-cardiac arrest patients in the ICU; (2) investigate associations between pain and pain management strategies with delirium and ICU resource utilization; and (3) explore the relationship between pain management, early neurological recovery, and longer-term patient-reported outcomes, including pain interference and quality of life.

PAINCARE is designed as an observational, prospective cohort substudy conducted within the framework of the STEPCARE randomized controlled trial. All patients enrolled in STEPCARE at centers participating in PAINCARE are eligible for inclusion in PAINCARE unless data on pain cannot be collected. No additional interventions are introduced by the substudy. Data are collected as part of routine ICU care and within the structure of the STEPCARE electronic case report form (eCRF). Participating centers include tertiary care hospitals and academic ICUs across multiple countries. Local investigators are responsible for ethical compliance and data quality.

The substudy uses the STEPCARE eCRF for standardized data entry and expands the dataset with variables related to pain and analgesia. Key domains include pain intensity and assessment (using validated behavioral or numeric scales), sedation parameters, delirium assessments, and clinical outcomes (ICU length of stay, duration of mechanical ventilation, in-hospital mortality). Patient-reported outcomes, including measures of pain interference and quality of life, will be collected at follow-up using standardized questionnaires. All data are entered into the eCRF by trained research staff, and automated validation checks ensure completeness, range conformity, and logical consistency.

The PAINCARE substudy follows the data management and quality assurance framework of the STEPCARE trial. A comprehensive quality assurance plan includes automated data checks, central data review, and periodic monitoring. Research staff and investigators receive standardized training and ongoing support to ensure consistency across sites.

PAINCARE is primarily descriptive and exploratory. The substudy will include all eligible STEPCARE participants for whom pain data are available, expected to total approximately 400 patients across sites. Descriptive statistics will summarize pain intensity, and outcomes. Multivariable regression models will be used to explore associations between pain-related variables and outcomes such as delirium, ICU stay, and long-term recovery, adjusting for covariates such as sedation depth, site, and baseline characteristics. Missing data will be evaluated, and multiple imputation techniques may be applied when appropriate. Sensitivity analyses will be performed to assess robustness of results. Analyses will be conducted after STEPCARE data collection is complete and main trial results have been published.

The substudy is observational and imposes no additional risk to participants. Ethical approval has been obtained in all participating countries according to local regulations. Informed consent follows the approved procedures of the STEPCARE trial. All data are de-identified before analysis, and confidentiality is maintained in accordance with applicable data protection laws, including the General Data Protection Regulation (GDPR) where relevant.

PAINCARE will provide a detailed description of pain and pain management practices in post-cardiac arrest patients and evaluate how these factors relate to delirium, ICU resource use, and patient-centered outcomes. The findings are expected to inform evidence-based strategies for pain assessment and management in the ICU, with the goal of improving comfort, reducing complications, and enhancing recovery for survivors of cardiac arrest.