A comparative study of targeted end-tidal carbon dioxide versus standard management to guide resuscitation in emergency department cardiac arrest in Thailand: study protocol for a three-arm randomised controlled trial

Cardiac arrest managed in the emergency department (ED) is associated with suboptimal survival outcomes. End-tidal carbon dioxide (EtCO 2 ) monitoring during cardiopulmonary resuscitation (CPR) reflects cardiac output, tissue perfusion, and pulmonary blood flow. Observational evidence suggests that higher EtCO 2 levels during CPR are associated with return of spontaneous circulation (ROSC), but the effect of actively targeting higher EtCO 2 thresholds remains uncertain. The primary objective of this trial is to determine whether CPR guided by higher EtCO 2 targets improves sustained ROSC compared with a standard EtCO 2 target among patients with ED cardiac arrest. This is a single-centre, three-arm, single-blind, superiority randomised controlled trial conducted in the ED of Thammasat University Hospital, Pathum Thani, Thailand. Eligible participants are patients with ED cardiac arrest, including out-of-hospital cardiac arrest patients receiving CPR in the ED and patients with first in-hospital cardiac arrest occurring in the ED. Exclusion criteria include age < 15 years, traumatic cardiac arrest, a do-not-attempt-resuscitation order, and signs of irreversible death. Post-randomisation exclusions include inability to obtain EtCO 2 monitoring through an advanced airway and ROSC before the first EtCO 2 measurement. Consecutive eligible participants will be screened and enrolled by the attending emergency physician. Participants will be randomised in a 1:1:1 ratio using fixed-block randomisation with a block size of six; no stratification variables will be used. The planned sample size is 300 participants, with 100 participants per group. All participants will receive high-quality CPR according to international resuscitation guidelines and will be assigned to one of three EtCO 2 targets: ≥ 10 mmHg, ≥ 20 mmHg, or ≥ 25% of venous partial pressure of carbon dioxide (PvCO 2 ), with a minimum threshold of 10 mmHg. Peripheral venous PvCO 2 will be obtained using point-of-care testing every 10 min. Chest compression depth and rate will be titrated in 0.5-cm and 10/min increments, respectively, every 30 s until the assigned EtCO 2 target is achieved. The primary outcome is sustained ROSC. Secondary outcomes include survival to hospital discharge and survival with favourable neurological outcome. Safety and harm measures include adverse events related to the study intervention, unanticipated device-related issues, and complications attributed to study-directed chest-compression adjustments. These events will be documented, reported to the coordinating centre and ethics committee as required, and reviewed by the Data Safety Monitoring Board. Analyses will follow both intention-to-treat and per-protocol principles. This trial will evaluate whether higher absolute or patient-specific EtCO 2 targets during CPR improve resuscitation outcomes compared with the standard EtCO 2 threshold in ED cardiac arrest patients. Thai Clinical Trials Registry (TCTR), TCTR20240619001, registered on 19 June 2024: https://www.thaiclinicaltrials.org/show/TCTR20240619001 .