Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock
Condition: New Onset Atrial Fibrillation; Severe Sepsis; Septic Shock
MeSH terms: Sepsis; Toxemia; Shock, Septic; Atrial Fibrillation; Shock
Intervention: Amiodarone
Intervention description: Patients will receive a 150 mg IV bolus amiodarone dose, followed by a 1 mg/min continuous infusion for six hours, then 0.5 mg/min. Conversion to PO amiodarone will be based on patient hemodynamic stability and physician/pharmacist discretion. The total loading dose will be calculated based on all IV and PO amiodarone administered within 7 days from initiation of amiodarone. All doses will be compared in total PO equivalents (accounting for 50% bioavailability of PO vs IV amiodarone). Randomization may be overridden by the attending or fellow physician if the patient's severity of illness warrants. Discontinuation of amiodarone in the full-load group will be at the discretion of the physician/pharmacists, after the pre-determined randomization loading dose has been provided.
Intervention MeSH terms: Amiodarone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Purpose/Objectives: Severe sepsis and septic shock are a common cause of new onset atrial
      fibrillation (NOAF) in the intensive care unit. Development of NOAF in this setting can
      prolong length of stay and increase mortality. Amiodarone is the most commonly used agent
      used in this setting to control rate and rhythm. However, limited data exist detailing
      appropriate dosing in this setting. The primary objective of this study is to evaluate two
      amiodarone dosing strategies, a full loading dose versus a partial loading dose, in patients
      with new-onset atrial fibrillation (AF) due to severe sepsis or septic shock to assess the
      mean heart rate every 6 hours after initiation of amiodarone infusion to day 7 or death.

      Research Design/Plan: Consecutive patients admitted to the medical or cardiac intensive care
      unit at University Hospital with NOAF in the setting of severe sepsis or septic shock will be
      screened for study inclusion. Data will be collected and stored using Microsoft Excel or
      Access and analyzed with JMP 12.0 and SPSS.

      Methods: 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. Patients will receive
      intravenous (IV) and oral (PO) amiodarone, as per the standard of care. Patients will be
      randomized to a certain quantitative loading dose strategy; either a full loading dose (≥ 5g
      IV or ≥10g PO +/- 20%) or a partial loading dose (<4g IV or < 8g PO).

      Clinical Relevance: With intensive care unit length of stay (ICU LOS) and mortality being
      twice as high in NOAF with sepsis as compared to septic patients without NOAF, the
      investigators ultimately aim to identify a management strategy that may minimize this
      morbidity and mortality while also minimizing exposure to a drug that may cause serious
      adverse effects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  New onset atrial fibrillation

          -  Severe sepsis or septic shock (defined by ≥2 systemic inflammatory response syndrome
             criteria + infection)

        Exclusion Criteria:

          -  Age < 18 years

          -  History of atrial flutter

          -  History of atrial fibrillation

          -  QTc >500 msec at baseline

          -  2nd or 3rd degree AV block

          -  Currently receiving anti-arrhythmic therapy

          -  Untreated thyroid dysfunction

          -  Acute or chronic hepatic failure

          -  Other indication for antiarrhythmic therapy

          -  Recent cardiac surgery in last 30 days

          -  Pregnancy