Feasibility and Cardiac Safety of Inhaled Xenon in Combination With Therapeutic Hypothermia Following Out-of-Hospital Cardiac Arrest

Objectives: Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. Design: An open controlled and randomized single-centre clinical drug trial (Clinicaltrials.gov NCT00879892). Setting: A multipurpose ICU in university hospital. Patients: Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm. Interventions: Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33 degrees C (mild therapeutic hypothermia group, n = 18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon + mild therapeutic hypothermia group, n = 18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n = 17; Xenon + mild therapeutic hypothermia group, n = 16). Measurements and Main Results: Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group = 5.30 mg vs Xenon + mild therapeutic hypothermia group = 2.95 mg, p = 0.06). Heart rate was significantly lower in Xenon + mild therapeutic hypothermia patients during hypothermia (p = 0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon + mild therapeutic hypothermia group (p = 0.04). Conclusions: Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.