Clinical trial NCT03413150: Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients With Atrial Tachyarrhythmias
Official title: Modeling of Amiodarone Effect on Heart Rate Control in Critically Ill Patients With Atrial Tachyarrhythmias
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Atrial Tachycardia
Lead sponsor: Groupe Hospitalier Pitie-Salpetriere
Sponsor class: OTHER
First posted: 2018-01-29
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Heart Rate
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Nicot F, Procopi N, Nguyen LS. Intravenous amiodarone-induced acute liver failure in cardiac surgery intensive care unit. Therapie. 2018 Sep;73(4):355-357. doi: 10.1016/j.therap.2017.12.007. Epub 2017 Dec 30. No abstract available.
citation: Artucio H, Pereira M. Cardiac arrhythmias in critically ill patients: epidemiologic study. Crit Care Med. 1990 Dec;18(12):1383-8. doi: 10.1097/00003246-199012000-00015.
citation: Packer DL, Bardy GH, Worley SJ, Smith MS, Cobb FR, Coleman RE, Gallagher JJ, German LD. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol. 1986 Mar 1;57(8):563-70. doi: 10.1016/0002-9149(86)90836-2.
citation: Nerheim P, Birger-Botkin S, Piracha L, Olshansky B. Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia. Circulation. 2004 Jul 20;110(3):247-52. doi: 10.1161/01.CIR.0000135472.28234.CC. Epub 2004 Jun 28.
citation: 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.
citation: 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.
citation: Kumar A. Intravenous amiodarone for therapy of atrial fibrillation and flutter in critically ill patients with severely depressed left ventricular function. South Med J. 1996 Aug;89(8):779-85. doi: 10.1097/00007611-199608000-00005.
citation: Clemo HF, Wood MA, Gilligan DM, Ellenbogen KA. Intravenous amiodarone for acute heart rate control in the critically ill patient with atrial tachyarrhythmias. Am J Cardiol. 1998 Mar 1;81(5):594-8. doi: 10.1016/s0002-9149(97)00962-4.
citation: Mayr A, Knotzer H, Mutz N, Hasibeder W. Atrial tachyarrhythmia after cardiac surgery. Intensive Care Med. 1999 Feb;25(2):242-3. doi: 10.1007/s001340050827. No abstract available.
citation: Galve E, Rius T, Ballester R, Artaza MA, Arnau JM, Garcia-Dorado D, Soler-Soler J. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. J Am Coll Cardiol. 1996 Apr;27(5):1079-82. doi: 10.1016/0735-1097(95)00595-1.
citation: 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.
citation: 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.
citation: 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.
citation: Donaldson L, Grant IS, Naysmith MR, Thomas JS. Acute amiodarone-induced lung toxicity. Intensive Care Med. 1998 Jun;24(6):626-30. doi: 10.1007/s001340050627.
citation: Ratz Bravo AE, Drewe J, Schlienger RG, Krahenbuhl S, Pargger H, Ummenhofer W. Hepatotoxicity during rapid intravenous loading with amiodarone: Description of three cases and review of the literature. Crit Care Med. 2005 Jan;33(1):128-34; discussion 245-6. doi: 10.1097/01.ccm.0000151048.72393.44.
citation: Papiris SA, Triantafillidou C, Kolilekas L, Markoulaki D, Manali ED. Amiodarone: review of pulmonary effects and toxicity. Drug Saf. 2010 Jul 1;33(7):539-58. doi: 10.2165/11532320-000000000-00000.
citation: Lafont E, Urien S, Salem JE, Heming N, Faisy C. Modeling for critically ill patients: An introduction for beginners. J Crit Care. 2015 Dec;30(6):1287-94. doi: 10.1016/j.jcrc.2015.09.002. Epub 2015 Sep 4.
citation: Tonet JL, Lechat P, Frank R, Lascault G, Fontaine G, Facquet J, Cohen A, Grosgogeat Y. [Electrocardiographic effects and antiarrhythmic action of 1200 mg of oral amiodarone per day]. Ann Cardiol Angeiol (Paris). 1984 Jul-Sep;33(5):309-15. French.
citation: Kochiadakis GE, Igoumenidis NE, Solomou MC, Kaleboubas MD, Chlouverakis GI, Vardas PE. Efficacy of amiodarone for the termination of persistent atrial fibrillation. Am J Cardiol. 1999 Jan 1;83(1):58-61. doi: 10.1016/s0002-9149(98)00783-8.
citation: Anastasiou-Nana M, Levis GM, Moulopoulos S. Pharmacokinetics of amiodarone after intravenous and oral administration. Int J Clin Pharmacol Ther Toxicol. 1982 Nov;20(11):524-9.
citation: Pourbaix S, Berger Y, Desager JP, Pacco M, Harvengt C. Absolute bioavailability of amiodarone in normal subjects. Clin Pharmacol Ther. 1985 Feb;37(2):118-23. doi: 10.1038/clpt.1985.22.
citation: 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.
citation: 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.
citation: Schwartz A, Shen E, Morady F, Gillespie K, Scheinman M, Chatterjee K. Hemodynamic effects of intravenous amiodarone in patients with depressed left ventricular function and recurrent ventricular tachycardia. Am Heart J. 1983 Oct;106(4 Pt 2):848-56. doi: 10.1016/0002-8703(83)90007-8.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Butterworth J. Dobutamine: too dangerous for "routine" administration? Anesthesiology. 2008 Jun;108(6):973-4. doi: 10.1097/ALN.0b013e318172fb98. No abstract available.
citation: 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.
citation: 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.
citation: Kanji S, Williamson DR, Yaghchi BM, Albert M, McIntyre L; Canadian Critical Care Trials Group. Epidemiology and management of atrial fibrillation in medical and noncardiac surgical adult intensive care unit patients. J Crit Care. 2012 Jun;27(3):326.e1-8. doi: 10.1016/j.jcrc.2011.10.011. Epub 2012 Jan 4.
citation: Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, Fletcher RD, Sharma SC, Atwood JE, Jacobson AK, Lewis HD Jr, Raisch DW, Ezekowitz MD; Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T) Investigators. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med. 2005 May 5;352(18):1861-72. doi: 10.1056/NEJMoa041705.
citation: Sticherling C, Behrens S, Kamke W, Stahn A, Zabel M. Comparison of acute and long-term effects of single-dose amiodarone and verapamil for the treatment of immediate recurrences of atrial fibrillation after transthoracic cardioversion. Europace. 2005 Nov;7(6):546-53. doi: 10.1016/j.eupc.2005.05.017. Epub 2005 Sep 30.
citation: Harris L, Hind CR, McKenna WJ, Savage C, Krikler SJ, Storey GC, Holt DW. Renal elimination of amiodarone and its desethyl metabolite. Postgrad Med J. 1983 Jul;59(693):440-2. doi: 10.1136/pgmj.59.693.440.
citation: Vietti-Ramus G, Veglio F, Marchisio U, Burzio P, Latini R. Efficacy and safety of short intravenous amiodarone in supraventricular tachyarrhythmias. Int J Cardiol. 1992 Apr;35(1):77-85. doi: 10.1016/0167-5273(92)90058-b.
citation: Brodsky MA, Allen BJ, Walker CJ 3rd, Casey TP, Luckett CR, Henry WL. Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium. Am J Cardiol. 1987 Sep 1;60(7):572-5. doi: 10.1016/0002-9149(87)90307-9.
citation: Kochiadakis GE, Igoumenidis NE, Parthenakis FI, Chlouverakis GI, Vardas PE. Amiodarone versus propafenone for conversion of chronic atrial fibrillation: results of a randomized, controlled study. J Am Coll Cardiol. 1999 Mar 15;33(4):966-71. doi: 10.1016/s0735-1097(98)00678-0.
citation: Greenberg ML, Lerman BB, Shipe JR, Kaiser DL, DiMarco JP. Relation between amiodarone and desethylamiodarone plasma concentrations and electrophysiologic effects, efficacy and toxicity. J Am Coll Cardiol. 1987 May;9(5):1148-55. doi: 10.1016/s0735-1097(87)80320-0.
citation: Deharo JC, Durand A, Macaluso G, Malaterre H, Le Tallec L, Panagides D, Bory M, Djiane P. Clinical electrophysiologic effects of a single high oral dose of amiodarone. Fundam Clin Pharmacol. 1997;11(3):275-80. doi: 10.1111/j.1472-8206.1997.tb00196.x.
citation: 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.
citation: 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.
citation: 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.