Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock

Step-by-Step Methods:

Population: The study will be conducted at University Hospital, the 716-bed county hospital for Bexar County and serves a varied population, including patients from medically underserved areas. The patient population will come from the medical intensive care unit and the cardiac intensive care unit, a 20 and 26-bed unit, respectively, at University Hospital that is the clinical practice and teaching site for one study investigator.

Screening: Consecutive patients admitted to the medical or cardiac intensive care unit at University Hospital with new onset atrial fibrillation in the setting of severe sepsis or septic shock will be screened for study inclusion. Participants will be 18 years or older. Patients who develop new-onset atrial fibrillation in the setting of severe sepsis or septic shock will be considered for study inclusion. Exclusion criteria apply to those younger than 18 years of age, those with a history of atrial flutter, baseline QTc (a measurement made on a electrocardiogram which measures the start of the Q wave to the end of the T wave) > 500 msec, atrial fibrillation during the index admission or in their past medical history, second or third degree atrioventricular (AV) block, those recovering from cardiac surgery done during the same hospital admission, those who have received amiodarone or other Vaughan Williams class I or III antiarrhythmic drugs in the last 6 months, untreated/poorly controlled hypothyroidism, hyperthyroidism, acute or chronic hepatic failure, other requirements of antiarrhythmic drug therapy, recent cardiac surgery in the preceding 30 days, and those who are pregnant.

Intervention: Patients aged 18 years or older who develop new-onset atrial fibrillation in the setting of severe sepsis or septic shock and in whom the medical team deems appropriate to initiate amiodarone therapy in will be considered for study inclusion. All patients will receive a 150 mg IV bolus dose of amiodarone, followed immediately by a continuous infusion of 1 mg/min for the first six hours, with a recommended reduction to 0.5 mg/min subsequently. Conversion from IV to PO amiodarone will occur based on patient hemodynamic stability and physician/pharmacist discretion. Patients will be randomized to receive amiodarone at a full loading dose (≥ 5g IV or ≥10g PO +/- 20%) or a partial loading dose (<4g IV or < 8g PO). The assigned total loading dose will include all IV and PO amiodarone administered within 7 days from initiation of amiodarone. All doses will be compared in total PO amount (accounting for 50% bioavailability of PO versus IV amiodarone). The primary attending or fellow physician may over-ride randomization if the patient's amiodarone dose if the patient's severity of illness warrants a duration that differs from that assigned during randomization. In the full loading dose group, discontinuation of amiodarone will be at the discretion of the physician/pharmacists, after the pre-determined randomization loading dose has been provided.

Management Components: Facilities to be used throughout the project include the University Hospital and The University of Texas Health Science Center at San Antonio. Equipment use for direct patient care will be in keeping with standards-of-care, without any additional equipment being required for the clinical research study.