Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients With Atrial Tachyarrhythmias

Study Overview
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Brief Summary
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Aims Amiodarone is the gold-standard medication to control heart rate in critically ill patients with atrial tachyarrhythmias (ATs); however, effective doses and covariates influencing its efficacy remain unknown. The investigators therefore performed pharmacodynamic modeling of heart rate reduction induced by amiodarone in these patients. Methods and Results This observational study included 80 consecutive severely ill patients receiving amiodarone to treat ATs. A total of 1348 time-heart rate observations with 361 amiodarone dose administrations were analyzed during a period of up to 6 days after hospital treatment initiation using a nonlinear mixed-effect model. Pretreatment with amiodarone before intensive care administration, paroxysmal versus persistent AT, catecholamine infusion, and fluid and magnesium loading were among the covariates assessed in the model. In case of paroxysmal AT in a patient not pretreated with amiodarone, a 300 mg intravenous loading dose combined with an 800 mg oral dose on the first day, followed by 800 mg/day orally for 4 days was effective in achieving a heart rate between 80 and 115 bpm within the first day, and to maintain it during the next 4 days. Corresponding doses were twice as high in patients with persistent AT. Use of intravenous magnesium (p\0.02) and fluid loading (p\0.02) was associated with an earlier and greater heart rate decrease, while use of dobutamine had an opposite influence (p\0.05). Conclusions In critically ill patients with AT, the dose of amiodarone required to control heart rate is influenced by the type of AT and by other easily measurable conditions which may allow better individualization of amiodarone dosing.

Official Title
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Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients With Atrial Tachyarrhythmias

Conditions
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Atrial Fibrillation, Atrial Tachycardia

Intervention / Treatment
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* Drug: Amiodarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: critically ill patients who had received at least one dose of amiodarone to treat or prevent AT during their hospitalization in the ICU. Exclusion Criteria: Patients with paced rhythm or incomplete charts were excluded
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| severely ill patients receiving amiodarone for ATs<br>cohort study was conducted from January 2007 to April 2012 in the 18-bed medical ICU of a tertiary teaching hospital.Data were extracted from the files of 80 consecutive critically ill patients who had received at least one dose of amiodarone to treat or prevent atrial tachycardia during their hospitalization in the ICU. | Drug: Amiodarone<br>* Data were extracted from the files of 80 consecutive critically ill patients who had received at least one dose of amiodarone to treat or prevent AT during their hospitalization in the ICU.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate | HR was retrieved from patients ICU charts | HR at 1rst administration of cordarone and then 4 to 6 times a day after each dosing until day 6 or death or ICU discharge |