Abstract
For hemodynamic stabilization of patients in a life-threatening situation such as septic or cardiogenic shock, the use of vasopressors, inotropics and sometimes inodilators is essential although not well supported by randomized studies. As the substances used have no effect on disease progression, they can only serve as hemodynamic „bridges” to gain time for causal therapies to act or until the bodies defense mechanisms have changed the course of the disease.
A differential therapeutic approach, which is useful and often necessary, takes the ventricular-arterial coupling of a damaged heart as well as the microcirculatory changes during shock, especially within the hepato-splanchnic tissue, into account.
During septic shock, inotropics and vasopressors are used in an evidence-based algorithm to achieve a timely optimization of the hemodynamic situation („early goal directed therapy”). To date, noradrenalin (alternatively, adrenalin or dopamine) and dobutamin are the inotropics of choice. During cardiogenic shock, however, only the concept of early revascularization and implantation of an intra-aortic counter pulsation is established by clinical studies. Therefore, pharmacologic stabilization can only serve to bridge the time to immediate coronary angiography and revascularization. In this situation, the use of dobutamin, if necessary in combination with noradrenalin, is judged clinically (RRsyst≥ 90 mmHg). After successful revascularization, however, pharmacologic therapy should be monitored and guided via extended hemodynamic monitoring (cardiac output, wedge pressure). Noradrenalin must be added, if arterial mean pressure remains < 65 mmHg despite an adequate fluid management, dobutamine use, and intra-aortic counter pulsation. Although currently not approved in Germany, the calcium-sensitizer levosimendan represents an interesting and potent therapeutic additive (or alternative) to achieve an adequate cardiac output. The (accurately timed) use of mechanical assist devices is only indicated after failure of above-mentioned recommendations.
Kernaussagen
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Zur hämodynamischen Stabilisierung lebensbedrohlicher Zustände wie dem septischen oder kardiogenen Schock ist der Einsatz von Vasopressoren, Inotropika und teilweise Inodilatoren essenziell, wenn auch in der Regel nicht durch große randomisierte Studien abgesichert.
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Diese Substanzen wirken nicht kausal heilend, sondern sie bauen „hämodynamische und zeitliche Brücken”, um die grundsätzliche Voraussetzung für den vollen Wirkeintritt ursächlicher Therapien oder körpereigener Erholungsmechanismen zu schaffen.
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Ein differenzieller Einsatz der Substanzen ist möglich und zumeist auch notwendig. Stets bedürfen hierbei die adäquate Kopplung von myokardialer Funktion und vaskulärer Nachlast (ventrikuloarterielle Kopplung) bei myokardialer Schädigung sowie die mikrovaskuläre Zirkulation, insbesondere im Hepatikosplanchnikusgebiet, besondere Beachtung.
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Beim septischen Schock ordnet sich die Gabe von Inotropika/Vasopressoren in einen evidenzbasierten Maßnahmenkatalog zur frühen Optimierung der Hämodynamik ein („early goal directed therapy”). Derzeit wird zumeist Noradrenalin als Vasopressor (alternativ Adrenalin, Dopamin) und Dobutamin als Inotropikum der Wahl bevorzugt.
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Beim kardiogenen Schock ist derzeit nur das Konzept der frühen Revaskularisierung sowie die frühe Implantation einer intraaortalen Gegenpulsation (IABP) durch Studien und große Register abgesichert. Die pharmakologische Strategie zur initialen Stabilisierung hat als primäres Ziel den sicheren und schnellen Zugang ins Herzkatheterlabor. Der Einsatz von Dobutamin, wenn nötig in Kombination mit Noradrenalin, wird klinisch gesteuert (RRsyst ≥ 90 mmHg). Nach der Revaskularisierung wird die weitere Therapie mittels erweiterten hämodynamischen Monitoring gesteuert. Bleibt der arterielle Mitteldruck trotz Vor- und Nachlastkorrektur und trotz Dobutamin und IABP weiter unter 65 mmHg, muss Noradrenalin eingesetzt werden. Um außerdem ein adäquates Herz-Zeit-Volumen zu generieren, existiert heute insbesondere mit dem Kalziumsensitizer Levosimendan (als Heilversuch, da bisher in Deutschland nicht zugelassen) eine sehr interessante und potente Therapiealternative. Der (rechtzeitige) Einsatz mechanischer Assistsysteme kommt erst nach Ausschöpfung der o. g. therapeutischen Kaskade infrage.
Literatur
-
1
Dellinger R P, Levy M M, Carlet J M. et al .
Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.
Crit Care Med.
2008;
36
296-327
-
2
Dickstein K, Cohen-Solal A, Filippatos G. et al .
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).
Eur Heart J.
2008;
29
2388-2442
-
3
Gauss A, Anhaupl T, Schutz W.
The basics of catecholamine therapy. 2. A guide to clinical use.
Anasthesiol Intensivmed Notfallmed Schmerzther.
2000;
35
131-136
-
4
Gillies M, Bellomo R, Doolan L, Buxton B.
Bench-to-bedside review: Inotropic drug therapy after adult cardiac surgery – a systematic literature review.
Crit Care.
2005;
9
266-279
-
5
Janssens U, Graf J.
Cardiovascular dysfunction in sepsis.
Anasthesiol Intensivmed Notfallmed Schmerzther.
2008;
43
56-63
-
6
Meier-Hellmann A.
Systemic and regional effects of vasoactive drugs.
Dtsch Med Wochenschr.
26 – 11 – 2004;
129
2616-2620
-
7
Schutz W, Anhaupl T, Gauss A.
Principles of catecholamine therapy. 1. Characterization of clinically relevant sympathomimetics.
Anasthesiol Intensivmed Notfallmed Schmerzther.
2000;
35
67-81
-
8
Overgaard C B, Dzavik V.
Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease.
Circulation.
2 – 9-2008;
118
1047-1056
-
9
Mebazaa A, Nieminen M S, Packer M. et al .
Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial.
JAMA.
2007;
297
1883-1891
-
10
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
-
11
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
-
12
Modest V E, Butterworth J F.
Effect of pH and lidocaine on beta-adrenergic receptor binding. Interaction during resuscitation?.
Chest.
1995;
108
1373-1379
-
13
Reynolds H R, Hochman J S.
Cardiogenic shock: current concepts and improving outcomes.
Circulation.
2008;
117
686-697
-
14
Hochman J S.
Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm.
Circulation.
2003;
107
2998-3002
-
15
Ruffolo Jr. R R.
The pharmacology of dobutamine.
Am J Med Sci.
1987;
294
244-248
-
16
Gheorghiade M, Gattis S W, Adams Jr. K F. et al .
The Pilot Randomized Study of Nesiritide Versus Dobutamine in Heart Failure (PRESERVD-HF).
Am J Cardiol.
2005;
96
18G-25G
-
17
Unverferth D A, Blanford M, Kates R E, Leier C V.
Tolerance to dobutamine after a 72 hour continuous infusion.
Am J Med.
1980;
69
262-266
-
18
Tune J D, Richmond K N, Gorman M W, Feigl E O.
Control of coronary blood flow during exercise.
Exp Biol Med (Maywood ).
2002;
227
238-250
-
19
Communal C, Singh K, Pimentel D R, Colucci W S.
Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway.
Circulation.
1998;
98
1329-1334
-
20
Singh K, Xiao L, Remondino A. et al .
Adrenergic regulation of cardiac myocyte apoptosis.
J Cell Physiol.
2001;
189
257-265
-
21
Denton M D, Chertow G M, Brady H R.
„Renal-dose” dopamine for the treatment of acute renal failure: scientific rationale, experimental studies and clinical trials.
Kidney Int.
1996;
50
4-14
-
22
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
-
23
Van den Berghe B G, de Zegher Z F.
Anterior pituitary function during critical illness and dopamine treatment.
Crit Care Med.
1996;
24
1580-1590
-
24
Holmes C L, Patel B M, Russell J A, Walley K R.
Physiology of vasopressin relevant to management of septic shock.
Chest.
2001;
120
989-1002
-
25
Salzman A L, Vromen A, Denenberg A, Szabo C.
K(ATP)-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock.
Am J Physiol.
1997;
272
H688-H694
-
26
Kusano E, Tian S, Umino T. et al .
Arginine vasopressin inhibits interleukin-1 beta-stimulated nitric oxide and cyclic guanosine monophosphate production via the V1 receptor in cultured rat vascular smooth muscle cells.
J Hypertens.
1997;
15
627-632
-
27
Hamu Y, Kanmura Y, Tsuneyoshi I, Yoshimura N.
The effects of vasopressin on endotoxin-induced attenuation of contractile responses in human gastroepiploic arteries in vitro.
Anesth Analg.
1999;
88
542-548
-
28
Haikala H, Kaivola J, Nissinen E.
Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan.
J Mol Cell Cardiol.
1995;
27
1859-1866
-
29
Jorgensen K, Bech-Hanssen O, Houltz E, Ricksten S E.
Effects of levosimendan on left ventricular relaxation and early filling at maintained preload and afterload conditions after aortic valve replacement for aortic stenosis.
Circulation.
2008;
117
1075-1081
-
30
Yokoshiki H, Sperelakis N.
Vasodilating mechanisms of levosimendan.
Cardiovasc Drugs Ther.
2003;
17
111-113
-
31
Rehberg S, Ertmer C, Van Aken A H. et al .
Role of Levosimendan in intensive care treatment of myocardial insufficiency.
Anaesthesist.
2007;
56
30-43
-
32
Ragaller M.
Microcirculation in sepsis and septic shock – therapeutic options?.
Anasthesiol Intensivmed Notfallmed Schmerzther.
2008;
43
48-53
-
33
Dickstein K, Cohen-Solal A, Filippatos G. et al .
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).
Eur Heart J.
2008;
29
2388-2442
-
34
Reinhart K, Brunkhorst F, Bone H. et al .
Diagnosis and therapy of sepsis. Guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine.
Internist (Berl).
2006;
47
356-358
-
35
Engel C, Brunkhorst F M, Bone H G. et al .
Epidemiology of sepsis in Germany: results from a national prospective multicenter study.
Intensive Care Med.
2007;
33
606-618
-
36
Ince C.
The microcirculation is the motor of sepsis.
Crit Care.
2005;
9 Suppl 4
13-19
-
37
Lam C, Tyml K, Martin C, Sibbald W.
Microvascular perfusion is impaired in a rat model of normotensive sepsis.
J Clin Invest.
1994;
94
2077-2083
-
38
Rivers E, Nguyen B, Havstad S. et al .
Early goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med.
2001;
345
1368-1377
-
39
Muller-Werdan U, Buerke M, Ebelt H. et al .
Septic cardiomyopathy – A not yet discovered cardiomyopathy?.
Exp Clin Cardiol.
2006;
11
226-236
-
40
Reinelt H, Radermacher P, Fischer G. et al .
Effects of a dobutamine-induced increase in splanchnic blood flow on hepatic metabolic activity in patients with septic shock.
Anesthesiology.
1997;
86
818-824
-
41
De Backer D, Creteur J, Dubois M J. et al .
The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects.
Crit Care Med.
2006;
34
403-408
-
42
Annane D, Vignon P, Renault A. et al .
Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial.
Lancet.
2007;
370
676-684
-
43
Bollaert P E, Bauer P, Audibert G. et al .
Effects of epinephrine on hemodynamics and oxygen metabolism in dopamine-resistant septic shock.
Chest.
1990;
98
949-953
-
44
Noto A, Giacomini M, Palandi A. et al .
Levosimendan in septic cardiac failure.
Intensive Care Med.
2005;
31
164-165
-
45
Oldner A, Konrad D, Weitzberg E. et al .
Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock.
Crit Care Med.
2001;
29
2185-2193
-
46
Sharshar T, Blanchard A, Paillard M. et al .
Circulating vasopressin levels in septic shock.
Crit Care Med.
2003;
31
1752-1758
-
47
O’Brien A, Clapp L, Singer M.
Terlipressin for norepinephrine-resistant septic shock.
Lancet.
2002;
359
1209-1210
-
48
Russell J A, Walley K R, Singer J. et al .
Vasopressin versus norepinephrine infusion in patients with septic shock.
N Engl J Med.
2008;
358
877-887
-
49
Hamm C W.
Guidelines: acute coronary syndrome (ACS). 1: ACS without persistent ST segment elevations.
Z Kardiol.
2004;
93
72-90
-
50
Van de Werf F, Bax J, Betriu A. et al .
Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology.
Eur Heart J.
2008;
29
2909-2945
-
51
Hochman J S, Sleeper L A, Webb J G. et al .
Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.
N Engl J Med.
1999;
341
625-634
-
52
Stone G W, Ohman E M, Miller M F. et al .
Contemporary utilization and outcomes of intra-aortic balloon counterpulsation in acute myocardial infarction: the benchmark registry.
J Am Coll Cardiol.
2003;
41
1940-1945
-
53
Sjauw K D, Engstrom A E, Vis M M. et al .
A systematic review and meta-analysis of intra aortic balloon pump therapy in ST-elevation myocardial infarction:should we change the guidelines?.
Eur Heart J.
2009;
30
459-468
-
54
Kurose M, Okamoto K, Sato T. et al .
Emergency and long-term extracorporeal life support following acute myocardial infarction: rescue from severe cardiogenic shock related to stunned myocardium.
Clin Cardiol.
1994;
17
552-557
-
55
Lim N, Dubois M J, De Backer D. et al .
Do all nonsurvivors of cardiogenic shock die with a low cardiac index?.
Chest.
2003;
124
1885-1891
-
56
Kohsaka S, Menon V, Lowe A M. et al .
Systemic inflammatory response syndrome after acute myocardial infarction complicated by cardiogenic shock.
Arch Intern Med.
2005;
165
1643-1650
-
57
Prondzinsky R, Werdan K, Buerke M.
Cardiogenic shock: pathophysiology, clinics, therapeutical options and perspectives.
Internist (Berl).
2004;
45
284-295
-
58
Buerke M, Russ M, Werdan K.
New pharmacological treatment approaches to cardiogenic shock.
Internist (Berl).
2007;
48
1442-1449
-
59
Janssens U, Graf J.
Systemic optimisation of oxygen-delivery – cardiac improvement.
Anasthesiol Intensivmed Notfallmed Schmerzther.
2005;
40
640-652
-
60
Russ M A, Prondzinsky R, Christoph A. et al .
Hemodynamic improvement following levosimendan treatment in patients with acute myocardial infarction and cardiogenic shock.
Crit Care Med.
2007;
35
2732-2739
-
61
Wunderlich C, Schober K, Schmeisser A. et al .
The adverse cardiopulmonary phenotype of caveolin-1 deficient mice is mediated by a dysfunctional endothelium.
J Mol Cell Cardiol.
2008;
44
938-947
-
62
De Backer D, Creteur J, Dubois M J. et al .
Microvascular alterations in patients with acute severe heart failure and cardiogenic shock.
Am Heart J.
2004;
147
91-99
-
63
Fuhrmann J T, Schmeisser A, Schulze M R. et al .
Levosimendan is superior to enoximone in refractory cardiogenic shock complicating acute myocardial infarction.
Crit Care Med.
2008;
36
2257-2266
-
64
Cotter G, Moshkovitz Y, Kaluski E. et al .
The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure.
Eur J Heart Fail.
2003;
5
443-451
-
65
Neviere R, Mathieu D, Chagnon J L. et al .
The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients.
Am J Respir Crit Care Med.
1996;
154
1684-1688
-
66
Silber S, Albertsson P, Aviles F F. et al .
Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology.
Eur Heart J.
2005;
26
804-847
-
67
Koreny M, Karth G D, Geppert A. et al .
Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction.
Am J Med.
2002;
112
115-119
PD Dr. med. Alexander Schmeisser
Universitätsklinikum Magdeburg
Klinik für Kardiologie, Angiologie und Pneumologie
Otto-von-Guericke Universität Magdeburg
Leipzigerstraße 44
39120 Magdeburg
eMail: Alexander.Schmeisser@med.orga.de
