Short summary

The DANOHCA trial is a multicenter, randomized controlled study evaluating four interventions for improvement of outcomes for comatose out-of-hospital cardiac arrest patients. The study evaluates two pharmacologic interventions, dexamethasone and olanzapine, and two physiological interventions, backrest position and early wake-up call. Pharmacological interventions will are double-blinded, while physiological interventions are be open-label. See www.danohca.dk for further information.

Rationale

Out-of-Hospital Cardiac Arrest (OHCA) affects approximately 5,400 individuals annually in Denmark, with a 30-day mortality rate exceeding 80%. Even among those resuscitated and admitted to intensive care units (ICUs), mortality remains around 50%. These patients often develop Post Cardiac Arrest Syndrome (PCAS), characterized by systemic inflammation, cerebral dysfunction, myocardial impairment, and the underlying cause of arrest, often coronary occlusion. Despite improved emergency care, many patients die due to irreversible brain injury, leading to withdrawal of life-sustaining therapy. To improve OHCA outcomes, multiple therapeutic targets need evaluation, including systemic inflammation, cerebral perfusion, sedation duration, and delirium prevention. The DANOHCA trial will assess four interventions: early high-dose steroid treatment, optimized backrest positioning, early wake-up call and extubation, and prophylactic olanzapine for delirium prevention. High-Dose Steroids for Systemic Inflammation Systemic inflammation following OHCA peaks within days and correlates with poor outcomes. Biomarkers such as IL-6, CRP, and TNF-alpha indicate severity of inflammation. While no definitive treatment exists, anti-inflammatory therapies, including IL-6 receptor antagonists and glucocorticoids, have shown promise. Small studies suggest potential survival and neurological benefits of glucocorticoids. Given their short-term safety profile, high-dose steroids may reduce inflammation, brain edema, and vasodilation. Optimizing Cerebral Perfusion with Backrest Positioning Elevating the backrest to 15-30 degrees reduces intracranial pressure and improves cerebral perfusion in brain injury patients. This strategy could benefit comatose OHCA patients with cerebral edema. The trial will compare an elevation of 35° in Semi-Fowler's position with a 5° reclined position for 72 hours post-resuscitation to determine its impact on cerebral perfusion and survival. Early Wake-Up and Extubation The optimal sedation duration for post-OHCA patients remains uncertain. While deep sedation may protect the brain, it also increases delirium risk, ventilator-associated pneumonia, and ICU stays. Traditional post-resuscitation care required sedation for at least 24 hours, but newer studies suggest TTM at 37.5°C can be managed without it. This study will compare early wake-up (≤6 hours) with standard extubation (28-36 hours) to assess safety and feasibility. Preventing Delirium with Olanzapine Delirium is common in critically ill patients, especially post-OHCA. While antipsychotics have not consistently improved treatment outcomes, prophylactic administration may help prevent its onset. Olanzapine, a multi-receptor-blocking antipsychotic, could reduce delirium and improve rehabilitation. This trial will evaluate whether early olanzapine administration lowers delirium incidence and improves recovery. The DANOHCA trial is a multicenter, randomized controlled study evaluating these four interventions. Pharmacological interventions (steroids and olanzapine) will be double-blinded, while physiological interventions (backrest position and early wake-up) will be open-label. Findings may help optimize post-OHCA care and improve survival and neurological outcomes.

Description of the cohort

Resuscitated out-of-hospital cardiac arrest patients who remain comatose at hospital admission and have a suspected cardiac cause of the arrest.

Data and biological material

OPEN will be utilized for storage of plasma and serum.

Collaborating researchers and departments

Rigshospitalet, Department of Cardiology, The Heart Centre, Copenhagen University Hospital

• Professor Christian Hassager, MD DMSc
• Jesper Kjærgaard, MD PhD DMSc
• Martin Meyer, MD PhD

Department of Intensive Care, Aalborg University Hospital, Aalborg

• Jo Boending Andreasen, MD PhD

Department of Intensive Care, Aarhus University Hospital, Aarhus.

• Anders Grejs, MD PhD

Department of Intensive Care, Zealand University Hospital, Koege Hospital, Koege

• Lars Peter Kloster Andersen, MD PhD