Download PDF
Pneumologie 2007; 61(11): 700-708
DOI: 10.1055/s-2007-980108
Serie: Intensivmedizin
© Georg Thieme Verlag Stuttgart · New York

Rationaler Einsatz von Katecholaminen und Inotropika

Rational Use of Catecholamines and InotropesB.  Hewing1 , K.  Stangl1
  • 1Universitätsmedizin Berlin, Medizinische Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie, Charité Campus Mitte, Berlin
Further Information

Publication History

Publication Date:
10 October 2007 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Akutes Herzversagen stellt mit allein 1 Mio. Fällen/Jahr in den USA ein zentrales medizinisches Problem dar. Während ein Teil der Patienten mit Strategien der Vor- und Nachlastsenkung durch Diuretika und Vasodilatatoren gut rekompensiert werden kann, stellt die Gruppe mit schwerer hämodynamischer Kompromittierung und weiter bestehender Hypoperfusion ein besonderes Problem dar (90 Tage Mortalität: 15 %). Zur Überwindung dieser Akutsituation wird der i. v. Einsatz von positiv inotropen Substanzen notwendig. Derzeit stehen als Inotropika Adrenorezeptor-Agonisten (Dopamin, Dobutamin, Noradrenalin, Adrenalin), Phosphodiesterase III Inhibitoren (Milrinon, Enoximon) und Ca2+-Sensitizer (Levosimendan) zur Verfügung. Der kurzfristigen hämodynamischen Verbesserung der ersten beiden Gruppen steht die Steigerung des myokardialen Sauerstoffverbrauchs, proarrhythmische Effekte und möglicherweise mittelfristig eine Exzessmortalität gegenüber. Dieses Review beleuchtet den Stellenwert der einzelnen Substanzen im Therapiekonzept des akuten Herzversagens und gibt einen Ausblick auf Neuentwicklungen wie Myosin-Aktivatoren und Na+/K+-ATPase-Inhibitoren.

Abstract

Acute heart failure syndromes (AHFS) are a growing health problem in Western Countries. Standard treatment includes vasodilators and diuretics, however, the subgroup of patients with AHFS and low cardiac output state represents a special therapeutic challenge that is complicated by high in-hospital and post-discharge mortality and by requiring additional i. v. inotropic support. The current inotropes in use are adrenoreceptor agonists (dopamine, dobutamine, norepinephrine, epinephrine), phosphodiesterase III inhibitors (milrinone, enoximone), and Ca2+ sensitizers (levosimendane). While most inotropes yield short-term haemodynamic improvements, they are associated with increased myocardial oxygen consumption, (supra-) ventricular arrhythmias and possibly increased post-discharge mortality. This review highlights current inotropes used in the treatment of AHFS and introduces new drug developments including myosin activators and Na+/K+ ATPase inhibitors.

Literatur

  • 1 Nieminen M S, Harjola V P. Definition and epidemiology of acute heart failure syndromes.  Am J Cardiol. 2005;  96 5G-10G
    Google Scholar
  • 2 Adams Jr. K F, Fonarow G C, Emerman C L. et al . Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE).  Am Heart J. 2005;  149 209-216
    Google Scholar
  • 3 Shin D D, Brandimarte F, De Luca L. et al . Review of current and investigational pharmacologic agents for acute heart failure syndromes.  Am J Cardiol. 2007;  99 4A-23A
    Google Scholar
  • 4 Gheorghiade M, Mebazaa A. Introduction to acute heart failure syndromes.  Am J Cardiol. 2005;  96 1G-4G
    Google Scholar
  • 5 Yano M, Ikeda Y, Matsuzaki M. Altered intracellular Ca2+ handling in heart failure.  J Clin Invest. 2005;  115 556-564
    Google Scholar
  • 6 Guimaraes S, Moura D. Vascular adrenoceptors: an update.  Pharmacol Rev. 2001;  53 319-356
    Google Scholar
  • 7 Brodde O E, Michel M C. Adrenergic and muscarinic receptors in the human heart.  Pharmacol Rev. 1999;  51 651-690
    Google Scholar
  • 8 Gauthier C, Leblais V, Kobzik L. et al . The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle.  J Clin Invest. 1998;  102 1377-1384
    Google Scholar
  • 9 Lehtonen L, Poder P. The utility of levosimendan in the treatment of heart failure.  Ann Med. 2007;  39 2-17
    Google Scholar
  • 10 Lohse M J, Engelhardt S, Eschenhagen T. What is the role of beta-adrenergic signaling in heart failure?.  Circ Res. 2003;  93 896-906
    Google Scholar
  • 11 Parissis J T, Farmakis D, Nieminen M. Classical inotropes and new cardiac enhancers.  Heart Fail Rev. 2007;  12 149-156
    Google Scholar
  • 12 Cohn J N, Levine T B, Olivari M T. et al . Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure.  N Engl J Med. 1984;  311 819-823
    Google Scholar
  • 13 Kiuchi K, Shannon R P, Komamura K. et al . Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure.  J Clin Invest. 1993;  91 907-914
    Google Scholar
  • 14 Engelhardt S, Bohm M, Erdmann E. et al . Analysis of beta-adrenergic receptor mRNA levels in human ventricular biopsy specimens by quantitative polymerase chain reactions: progressive reduction of beta 1-adrenergic receptor mRNA in heart failure.  J Am Coll Cardiol. 1996;  27 146-154
    Google Scholar
  • 15 Freedman N J, Liggett S B, Drachman D E. et al . Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase.  J Biol Chem. 1995;  270 17 953-17 961
    Google Scholar
  • 16 Chakraborti S, Chakraborti T, Shaw G. beta-adrenergic mechanisms in cardiac diseases: a perspective.  Cell Signal. 2000;  12 499-513
    Google Scholar
  • 17 Lamba S, Abraham W T. Alterations in adrenergic receptor signaling in heart failure.  Heart Fail Rev. 2000;  5 7-16
    Google Scholar
  • 18 O’Rourke B, Kass D A, Tomaselli G F. et al . Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies.  Circ Res. 1999;  84 562-570
    Google Scholar
  • 19 Fowler M B, Laser J A, Hopkins G L. et al . Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response.  Circulation. 1986;  74 1290-1302
    Google Scholar
  • 20 Gheorghiade M, De Luca L, Fonarow G C. et al . Pathophysiologic targets in the early phase of acute heart failure syndromes.  Am J Cardiol. 2005;  96 11G-17G
    Google Scholar
  • 21 Osadchii O E. Cardiac hypertrophy induced by sustained beta-adrenoreceptor activation: pathophysiological aspects.  Heart Fail Rev. 2007;  12 66-86
    Google Scholar
  • 22 Dorn G W, Force T. Protein kinase cascades in the regulation of cardiac hypertrophy.  J Clin Invest. 2005;  115 527-537
    Google Scholar
  • 23 Nieminen M S, Bohm M, Cowie M R. et al . Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology.  Eur Heart J. 2005;  26 384-416
    Google Scholar
  • 24 Bellomo R, Chapman M, Finfer S. et al . Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group.  Lancet. 2000;  356 2139-2143
    Google Scholar
  • 25 Maskin C S, Ocken S, Chadwick B. et al . Comparative systemic and renal effects of dopamine and angiotensin-converting enzyme inhibition with enalaprilat in patients with heart failure.  Circulation. 1985;  72 846-852
    Google Scholar
  • 26 Debaveye Y A, Berghe G H Van den. Is there still a place for dopamine in the modern intensive care unit?.  Anesth Analg. 2004;  98 461-468
    Google Scholar
  • 27 Ruffolo Jr. R R, Spradlin T A, Pollock G D. et al . Alpha and beta adrenergic effects of the stereoisomers of dobutamine.  J Pharmacol Exp Ther. 1981;  219 447-452
    Google Scholar
  • 28 Burger A J, Horton D P, LeJemtel T. et al . Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study.  Am Heart J. 2002;  144 1102-1108
    Google Scholar
  • 29 O’Connor C M, Gattis W A, Uretsky B F. et al . Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST).  Am Heart J. 1999;  138 78-86
    Google Scholar
  • 30 Liang C S, Sherman L G, Doherty J U. et al . Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine.  Circulation. 1984;  69 113-119
    Google Scholar
  • 31 Krell M J, Kline E M, Bates E R. et al . Intermittent, ambulatory dobutamine infusions in patients with severe congestive heart failure.  Am Heart J. 1986;  112 787-791
    Google Scholar
  • 32 Lowes B D, Tsvetkova T, Eichhorn E J. et al . Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol.  Int J Cardiol. 2001;  81 141-149
    Google Scholar
  • 33 Leier C V. Positive inotropic therapy: an update and new agents.  Curr Probl Cardiol. 1996;  21 521-581
    Google Scholar
  • 34 Jain P, Massie B M, Gattis W A. et al . Current medical treatment for the exacerbation of chronic heart failure resulting in hospitalization.  Am Heart J. 2003;  145 S3-17
    Google Scholar
  • 35 Baumann G, Felix S B, Filcek S A. Usefulness of dopexamine hydrochloride versus dobutamine in chronic congestive heart failure and effects on hemodynamics and urine output.  Am J Cardiol. 1990;  65 748-754
    Google Scholar
  • 36 Perrin G, Papazian L, Martin C. [Dopexamine: a new dopaminergic agonist].  Ann Fr Anesth Reanim. 1993;  12 308-320
    Google Scholar
  • 37 Leier C V, Binkley P F. Parenteral inotropic support for advanced congestive heart failure.  Prog Cardiovasc Dis. 1998;  41 207-224
    Google Scholar
  • 38 Packer M, Carver J R, Rodeheffer R J. et al . Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group.  N Engl J Med. 1991;  325 1468-1475
    Google Scholar
  • 39 Cleland J G, Coletta A P, Lammiman M. et al . Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE.  Eur J Heart Fail. 2005;  7 1070-1075
    Google Scholar
  • 40 Cuffe M S, Califf R M, Adams Jr. K F. et al . Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial.  JAMA. 2002;  287 1541-1547
    Google Scholar
  • 41 Lalukota K, Cleland J G, Ingle L. et al . Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD.  Eur J Heart Fail. 2004;  6 953-955
    Google Scholar
  • 42 Gheorghiade M, Veldhuisen D J van, Colucci W S. Contemporary use of digoxin in the management of cardiovascular disorders.  Circulation. 2006;  113 2556-2564
    Google Scholar
  • 43 Haikala H, Nissinen E, Etemadzadeh E. et al . Troponin C-mediated calcium sensitization induced by levosimendan does not impair relaxation.  J Cardiovasc Pharmacol. 1995;  25 794-801
    Google Scholar
  • 44 Pagel P S, Harkin C P, Hettrick D A. et al . Levosimendan (OR-1259), a myofilament calcium sensitizer, enhances myocardial contractility but does not alter isovolumic relaxation in conscious and anesthetized dogs.  Anesthesiology. 1994;  81 974-987
    Google Scholar
  • 45 Jamali I N, Kersten J R, Pagel P S. et al . Intracoronary levosimendan enhances contractile function of stunned myocardium.  Anesth Analg. 1997;  85 23-29
    Google Scholar
  • 46 Moiseyev V S, Poder P, Andrejevs N. et al . Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN).  Eur Heart J. 2002;  23 1422-1432
    Google Scholar
  • 47 Follath F, Cleland J G, Just H. et al . Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial.  Lancet. 2002;  360 196-202
    Google Scholar
  • 48 Coletta A P, Cleland J G, Freemantle N. et al . Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy.  Eur J Heart Fail. 2004;  6 673-676
    Google Scholar
  • 49 Parissis J T, Farmakis D, Bistola V. et al . Levosimendan for the treatment of acute heart failure syndromes: time to identify subpopulations of responding patients.  Am J Cardiol. 2007;  99 146-147
    Google Scholar
  • 50 Kivikko M, Antila S, Eha J. et al . Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure.  Int J Clin Pharmacol Ther. 2002;  40 465-471
    Google Scholar
  • 51 Lee L, Campbell R, Scheuermann-Freestone M. et al . Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.  Circulation. 2005;  112 3280-3288
    Google Scholar
  • 52 Roberts R K, Cohn D, Petroff V. et al . Liver disease induced by perhexiline maleate.  Med J Aust. 1981;  2 553-554
    Google Scholar
  • 53 Bouche P, Bousser M G, Peytour M A. et al . Perhexiline maleate and peripheral neuropathy.  Neurology. 1979;  29 739-743
    Google Scholar
  • 54 Adamson P B, Vanoli E, Mattera G G. et al . Hemodynamic effects of a new inotropic compound, PST-2744, in dogs with chronic ischemic heart failure.  J Cardiovasc Pharmacol. 2003;  42 169-173
    Google Scholar
  • 55 Rocchetti M, Besana A, Mostacciuolo G. et al . Modulation of sarcoplasmic reticulum function by Na+/K+ pump inhibitors with different toxicity: digoxin and PST2744 [(E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride].  J Pharmacol Exp Ther. 2005;  313 207-215
    Google Scholar
  • 56 Meissner A, Herrmann G, Gerdesmeyer L. et al . Additive effects of milrinone and dobutamine in severe heart failure.  Z Kardiol. 1992;  81 266-271
    Google Scholar
  • 57 Cavusoglu Y. The use of levosimendan in comparison and in combination with dobutamine in the treatment of decompensated heart failure.  Expert Opin Pharmacother. 2007;  8 665-677
    Google Scholar
  • 58 Gilbert E M, Hershberger R E, Wiechmann R J. et al . Pharmacologic and hemodynamic effects of combined beta-agonist stimulation and phosphodiesterase inhibition in the failing human heart.  Chest. 1995;  108 1524-1532
    Google Scholar
  • 59 Haraldsson A, Kieler-Jensen N, Ricksten S E. The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension.  Anesth Analg. 2001;  93 1439-1445, table
    Google Scholar
  • 60 Hoeper M M, Olschewski H, Ghofrani H A. et al . A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group.  J Am Coll Cardiol. 2000;  35 176-182
    Google Scholar
  • 61 Beale R J, Hollenberg S M, Vincent J L. et al . Vasopressor and inotropic support in septic shock: an evidence-based review.  Crit Care Med. 2004;  32 S455-S465
    Google Scholar
  • 62 Martin C, Viviand X, Leone M. et al . Effect of norepinephrine on the outcome of septic shock.  Crit Care Med. 2000;  28 2758-2765
    Google Scholar
  • 63 Cleland J G, Freemantle N, Coletta A P. et al . Clinical trials update from the American Heart Association: REPAIR-AMI, ASTAMI, JELIS, MEGA, REVIVE-II, SURVIVE, and PROACTIVE.  Eur J Heart Fail. 2006;  8 105-110
    Google Scholar

Prof. Dr. med. Karl Stangl

Universitätsmedizin Berlin, Medizinische Klinik und Poliklinik mit Schwerpunkt Kardiologie und Angiologie, Charité Campus Mitte

Charitéplatz 1

10098 Berlin

Email: karl.stangl@charite.de

      >