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CompletedNCT03413150AMIRAUpdated Sep 26, 2019

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

An observational study in Atrial Fibrillation and Atrial Tachycardia, sponsored by Groupe Hospitalier Pitie-Salpetriere. Completed. Per ClinicalTrials.gov, last updated 2019-09-26.

Sponsored by Groupe Hospitalier Pitie-Salpetriere · Observational

Study type
Observational
Model
Cohort
Time perspective
Retrospective
Enrollment
80
Sex
All
01

Study summary

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.

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Conditions studied

  • Atrial Fibrillation
  • Atrial Tachycardia
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Critically ill patients who had received at least one dose of amiodarone to treat or prevent AT during their hospitalization from January 2007 to April 2012 in the 18-bed medical ICU of a tertiary teaching hospital

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

Exclusion Criteria:

  • Patients with paced rhythm or incomplete charts were excluded
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Study design

Observational model
Cohort
Time perspective
Retrospective
Enrollment
80 participants (actual)
Patient registry
No

Groups and cohorts

  • severely ill patients receiving amiodarone for ATs

    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

Interventions

  • DrugAmiodarone

    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.

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What researchers measure

Primary outcomes

  1. Heart Rate

    HR was retrieved from patients ICU charts

    Time frame: 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

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Study locations

No study locations are listed for this record.

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References and documents

Publications

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  • European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369-429. doi: 10.1093/eurheartj/ehq278. Epub 2010 Aug 29. No abstract available. Erratum In: Eur Heart J. 2011 May;32(9):1172. PubMed 20802247 ↗
  • January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014 Dec 2;130(23):2071-104. doi: 10.1161/CIR.0000000000000040. Epub 2014 Mar 28. No abstract available. Erratum In: Circulation. 2014 Dec 2;130(23):e270-1. PubMed 24682348 ↗
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  • Delle Karth G, Geppert A, Neunteufl T, Priglinger U, Haumer M, Gschwandtner M, Siostrzonek P, Heinz G. Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Crit Care Med. 2001 Jun;29(6):1149-53. doi: 10.1097/00003246-200106000-00011. PubMed 11395591 ↗
  • Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, Walter S, Tebbe U; STAF Investigators. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol. 2003 May 21;41(10):1690-6. doi: 10.1016/s0735-1097(03)00332-2. PubMed 12767648 ↗
  • Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ; Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002 Dec 5;347(23):1834-40. doi: 10.1056/NEJMoa021375. PubMed 12466507 ↗
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  • Vardas PE, Kochiadakis GE, Igoumenidis NE, Tsatsakis AM, Simantirakis EN, Chlouverakis GI. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study. Chest. 2000 Jun;117(6):1538-45. doi: 10.1378/chest.117.6.1538. PubMed 10858380 ↗
  • Lotto A, Satolli R, Baldini MR. Hemodynamic effects of amiodarone. Circulation. 1980 Sep;62(3):666. doi: 10.1161/01.cir.62.3.666. No abstract available. PubMed 7398031 ↗
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  • Remme WJ, Kruyssen HA, Look MP, van Hoogenhuyze DC, Krauss XH. Hemodynamic effects and tolerability of intravenous amiodarone in patients with impaired left ventricular function. Am Heart J. 1991 Jul;122(1 Pt 1):96-103. doi: 10.1016/0002-8703(91)90764-9. PubMed 2063768 ↗
  • Jacqmin P, Snoeck E, van Schaick EA, Gieschke R, Pillai P, Steimer JL, Girard P. Modelling response time profiles in the absence of drug concentrations: definition and performance evaluation of the K-PD model. J Pharmacokinet Pharmacodyn. 2007 Feb;34(1):57-85. doi: 10.1007/s10928-006-9035-z. Epub 2006 Oct 19. PubMed 17051439 ↗
  • Evans SJ, Myers M, Zaher C, Simonson J, Nalos P, Vaughn C, Oseran D, Gang E, Peter T, Mandel W. High dose oral amiodarone loading: electrophysiologic effects and clinical tolerance. J Am Coll Cardiol. 1992 Jan;19(1):169-73. doi: 10.1016/0735-1097(92)90069-y. PubMed 1729329 ↗
  • Hainsworth R. Reflexes from the heart. Physiol Rev. 1991 Jul;71(3):617-58. doi: 10.1152/physrev.1991.71.3.617. No abstract available. PubMed 2057525 ↗
  • Fellahi JL, Parienti JJ, Hanouz JL, Plaud B, Riou B, Ouattara A. Perioperative use of dobutamine in cardiac surgery and adverse cardiac outcome: propensity-adjusted analyses. Anesthesiology. 2008 Jun;108(6):979-87. doi: 10.1097/ALN.0b013e318173026f. PubMed 18497597 ↗
  • Butterworth J. Dobutamine: too dangerous for "routine" administration? Anesthesiology. 2008 Jun;108(6):973-4. doi: 10.1097/ALN.0b013e318172fb98. No abstract available. PubMed 18497594 ↗
  • Miller S, Crystal E, Garfinkle M, Lau C, Lashevsky I, Connolly SJ. Effects of magnesium on atrial fibrillation after cardiac surgery: a meta-analysis. Heart. 2005 May;91(5):618-23. doi: 10.1136/hrt.2004.033811. PubMed 15831645 ↗
  • Mayr A, Ritsch N, Knotzer H, Dunser M, Schobersberger W, Ulmer H, Mutz N, Hasibeder W. Effectiveness of direct-current cardioversion for treatment of supraventricular tachyarrhythmias, in particular atrial fibrillation, in surgical intensive care patients. Crit Care Med. 2003 Feb;31(2):401-5. doi: 10.1097/01.CCM.0000048627.39686.79. PubMed 12576943 ↗
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  • Patsilinakos S, Christou A, Kafkas N, Nikolaou N, Antonatos D, Katsanos S, Spanodimos S, Babalis D. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol. 2010 Sep 1;106(5):673-6. doi: 10.1016/j.amjcard.2010.04.020. Epub 2010 Jul 23. PubMed 20723644 ↗
  • Salem JE, Dureau P, Funck-Brentano C, Hulot JS, El-Aissaoui M, Aissaoui N, Urien S, Faisy C. Effectiveness of heart rate control on hemodynamics in critically ill patients with atrial tachyarrhythmias managed by amiodarone. Pharmacol Res. 2017 Aug;122:118-126. doi: 10.1016/j.phrs.2017.06.004. Epub 2017 Jun 10. PubMed 28610957 ↗
  • Salem JE, El-Aissaoui M, Alazard M, Hulot JS, Aissaoui N, Le-Heuzey JY, Funck-Brentano C, Faisy C, Urien S. Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients with Atrial Tachyarrhythmias. Clin Pharmacokinet. 2016 Aug;55(8):991-1002. doi: 10.1007/s40262-016-0372-9. PubMed 26946135 ↗

Individual participant data

Plan to share: No

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Registry details

Key details

Study ID
NCT03413150
Lead sponsor
Groupe Hospitalier Pitie-Salpetriere
Responsible party
Joe Elie Salem (MD, Groupe Hospitalier Pitie-Salpetriere) — Principal investigator
First posted
Jan 29, 2018
Start date
Jan 2007
Primary completion
Apr 2012
Completion
Apr 2012
Last update
Sep 26, 2019

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
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