This project is a randomized controlled clinical research design, The hypothesis P-I-C-O of the study is: For adult patients in the Taipei City and New Taipei City communities who have suffered sudden non-traumatic death and have been resuscitated by advanced paramedics, the intervention group that receives combined drug treatment (epinephrine, vasopressin, methylprednisolone) has a better rate of sustained recovery of spontaneous circulation (ROSC) (primary outcome) and long-term survival status (secondary outcomes) compared to the control group that receives single drug treatment (epinephrine).

The global and Taiwanese survival rates for patients following an out-of-hospital cardiac arrest (OHCA) are less than 10%. The emergency medical system (EMS) plays a crucial role in patient outcomes after OHCA, providing prehospital cardiopulmonary resuscitation, defibrillation, and medication. Among these medications, the combination of epinephrine, vasopressin, and methylprednisolone holds the most potential to improve patient survival rates following OHCA.

This study aims to compare the effect of standard epinephrine therapy with a combination of epinephrine, vasopressin, and methylprednisolone administered to OHCA patients. This comparison will be made through a randomized clinical trial (RCT) within the EMS of Taipei City and New Taipei City.

Throughout the research plan, we will conduct a prehospital RCT to answer the following question (in P-I-C-O format): Will adult non-traumatic OHCA patients resuscitated by paramedics in a prehospital setting have a better chance of sustained recovery of spontaneous circulation (primary outcome), and improved survival status (secondary outcomes), if they receive combination therapy (i.e., standard doses of epinephrine, 20U of vasopressin after each dose of epinephrine up to a maximum of 80U, and one dose of 40mg methylprednisolone after the first dose of epinephrine) compared to those who receive standard doses of epinephrine? We estimate a sample size of 1,344 OHCA patients to detect a difference in the primary outcome. Based on the background data from the EMS regions under study, we expect the enrollment to take approximately 30 months to complete.

This study is referred to as the "OHCA-REVIVES" trial, which stands for A randomized clinical trial of patient outcomes following Out-of-Hospital Cardiac Arrest Receiving Epinephrine Versus In-together Vasopressin, Epinephrine, and Steroid. The anticipated results from the "OHCA-REVIVES trial" will help determine the optimal strategy for prehospital medication, and will undoubtedly have a significant impact on resuscitation science. Through these efforts, we aim to improve the outcomes of OHCA patients.

Inclusion Criteria:

• Adult patients (aged >= 18 )
• Out-of-hospital cardiac arrest in the studied regions
• Treated by paramedics authorized and capable of giving prehospital medication

Exclusion Criteria:

• OHCA with traumatic etiology
• Obvious signs of death like decapitation, rigor mortis, livor mortis, decomposition, etc.
• DNR (Do Not Resuscitation) or termination of resuscitation requested by the family
• Patients with known or suspected pregnancy
• No vascular access was established before hospital arrival
• ROSC before the administrated medication
• No patient contact (cancelled ambulance call or the patient was transported to the hospital before the arrival of trial-trained paramedics)
• Received epinephrine prior to the arrival of trial-trained paramedics

Upon completion of the study, the sharing of Individual Participant Data (IPD) will be made available in accordance with local privacy protection laws.

Upon completion of the study, estimated at the end of 2026, the sharing of Individual Participant Data (IPD) will be made available following local privacy protection laws.

reasonable request to the corresponding authors.

Participant: adult patients with OHCA Outcomes Assessor: in-hospital care providers (physicians, nurses...etc)