title: Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients with Atrial Tachyarrhythmias.
abstract: 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. We therefore performed pharmacodynamic modeling of heart rate reduction induced by amiodarone in these patients.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Pharmacology and CIC-1421, AP-HP, Pitié-Salpêtrière Hospital, Paris, France. joe-elie.salem@aphp.fr.|Faculty of Medicine, INSERM UMRS ICAN-1166, Sorbonne Universités, UPMC Univ Paris 06, Paris, France. joe-elie.salem@aphp.fr.|Department of Cardiology-Rythmology Unit, AP-HP, Pitié-Salpêtrière Hospital, 75013, Paris, France. joe-elie.salem@aphp.fr.|Centre d'Investigation Clinique Paris-Est, Hôpital La Pitié-Salpêtrière, Bâtiment Antonin Gosset, 47-83 Bld de l'hôpital, 75651, Paris Cedex 13, France. joe-elie.salem@aphp.fr.
authors.forename: Joe-Elie
authors.initials: JE
authors.lastname: Salem
authors.affiliation: Critical Care Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Maria
authors.initials: M
authors.lastname: El-Aissaoui
authors.affiliation: Faculty of Medicine, INSERM UMRS ICAN-1166, Sorbonne Universités, UPMC Univ Paris 06, Paris, France.|Department of Cardiology-Rythmology Unit, AP-HP, Pitié-Salpêtrière Hospital, 75013, Paris, France.
authors.forename: Margaux
authors.initials: M
authors.lastname: Alazard
authors.affiliation: Department of Pharmacology and CIC-1421, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.|Faculty of Medicine, INSERM UMRS ICAN-1166, Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.affiliation: Critical Care Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Aissaoui
authors.affiliation: Cardiology-Rythmology Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le-Heuzey
authors.affiliation: Department of Pharmacology and CIC-1421, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.|Faculty of Medicine, INSERM UMRS ICAN-1166, Sorbonne Universités, UPMC Univ Paris 06, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Funck-Brentano
authors.affiliation: Centre d'Investigation Clinique-1419 INSERM, EAU-08 Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Faisy
authors.affiliation: Centre d'Investigation Clinique-1419 INSERM, EAU-08 Université Paris Descartes Sorbonne Paris Cité, Paris, France.
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000188:drug therapy; D015331:Cohort Studies; D016638:Critical Illness / Q000628:therapy*; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology; D015195:Drug Design; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology; D013610:Tachycardia / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D013566:Sympathomimetics; D004280:Dobutamine; D008278:Magnesium Sulfate; D000638:Amiodarone