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Cardiogenic Shock Due to Myocardial Infarction:
Diagnosis, Monitoring and Treatment
A German-Austrian S3 Guideline
Karl Werdan, Martin Ruß, Michael Buerke, Georg Delle-Karth, Alexander Geppert, Friedrich A. Schöndube Provided they reach hospital, patients with acute
myocardial infarction have a more than 90% Introduction: Infarction-related cardiogenic shock (ICS) is usually due to left- probability of surviving (1). If cardiogenic shock devel- ventricular pump failure. With a mortality of 30% to 80%, ICS is the most common cause of death from acute myocardial infarction. The S3 guideline ops, however, whether initially or in the course of the presented here characterizes the current evidence-based treatment of ICS: infarction, only one in two survives (2). All the early revascularization, treatment of shock, and intensive care treatment of progress made in the treatment of myocardial infarction multi-organ dysfunction syndrome (MODS) if it arises. The success or failure of seems to have ground to a halt before these 5% to 10% treatment for MODS determines the outcome in ICS.
of heart attack patients: The publication of the most im- Methods: Experts from eight German and Austrian specialty societies analyzed portant evidence-based progress in treatment of pa- approximately 3600 publications that had been retrieved by a systematic litera- tients with infarction-related cardiogenic shock ture search. Three interdisciplinary consensus conferences were held, resulting (ICS)—the earliest possible reperfusion of the infarcted in the issuing of 111 recommendations and algorithms for this S3 guideline.
vessel by percutaneous coronary intervention (PCI)—is Results: Early revascularization of the occluded vessel, usually with a percu - already more than 10 years old (3). taneous coronary intervention (PCI), is of paramount importance. The medical One main cause of the high mortality among patients treatment of shock consists of dobutamine as the inotropic agent and norepi- with ICS is the development of prolonged shock nephrine as the vasopressor of choice and is guided by a combination of pres - leading to multiorgan dysfunction syndrome (MODS) sure and flow values, or by the cardiac power index. Levosimendan can be (4). Consequently, ICS is not just a disease of the heart, given in addition to treat catecholamine-resistant shock. For patients with ICS but a disease of all the organs of the patient, who who are treated with PCI, the current S3 guideline differs from the European and American myocardial infarction guidelines with respect to the recommen- requires intensive care.
dation for intra-aortic balloon pulsation (IABP): Whereas the former guidelines The current European (5) and American myocardial give a class I recommendation for IABP, this S3 guideline states only that IABP infarction guidelines focus their recommendations on "can" be used in this situation, in view of the poor state of the evidence. Only "cardiological" treatment of the coronary arteries and for patients being treated with systemic fibrinolysis is IABP weakly recom- the cardiovascular system; the "intensive care medi- mended (IABP "should" be used in such cases). With regard to the optimal in- cine" treatment of MODS is little regarded. This deficit tensive-care interventions for the prevention and treatment of MODS, recom- motivated German and Austrian cardiologists, intensiv- mendations are given concerning ventilation, nutrition, erythrocyte-concentrate ists, cardiac surgeons, anesthetists, and rehabilitation transfusion, prevention of thrombosis and stress ulcers, follow-up care, and re-habilitation. specialists, together with their professional associ-ations, to develop an S3 guideline for "infarction- Discussion: The goal of this S3 guideline is to bring together the types of treat- related cardiogenic shock", under the auspices of the ment for ICS that lie in the disciplines of cardiology and intensive-care medi-cine, as patients with ICS die not only of pump failure, but also (and even more Association of Scientific Medical Societies in Germany frequently) of MODS. This is the first guideline that adequately emphasizes the (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen significance of MODS as a determinant of the outcome of ICS. Medizinischen Fachgesellschaften). The aim of this German-Austrian guideline, with its seven algorithms Cite this as: Werdan K, Ruß M, Buerke M, Delle-Karth G, Geppert A, Schöndube FA: Cardio- and 111 recommendations, is to provide an adequate genic shock due to myocardial infarction: diagnosis, monitoring and treatment. picture of both the cardiological and the intensive care A German-Austrian S3 guideline. Dtsch Arztebl Int 2012; 109(19): 343–51. aspects of this syndrome, since the prognosis of pa- tients with ICS depends not only on the impaired car-diac function, but, much more, on the resulting impair- Department of Internal Medicine III, University Hospital of Halle (Saale): Prof. Dr. med. Werdan ment of organ blood supply and microcirculation with Department of Internal Medicine I, Amper Kliniken AG, Dachau: Dr. med. Ruß consequent MODS.
Department of Cardiology and Angiology, St. Marien-Krankenhaus Siegen: Prof. Dr. med. Buerke The full version and the guideline report are avail- Department of Internal Medicine II, University Clinic at the Vienna General Hospital: able at (in German).
Prof. Dr. med. Delle-Karth Shortened print versions have so far appeared in the Intensive Care Unit, 3rd Medical Department/Cardiology, Wilhelminenspital, Vienna: Doz. Dr. med. Geppert journals Intensivmedizin und Notfallmedizin, Intensiv- University Medical Center Göttingen, Department of Thoracic and Cardiovascular Surgery: Prof. Dr. med. Schöndube und Notfallbehandlung, and Kardiologe (6).
Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 Medical societies and experts involved in guideline development
Deutsche Gesellschaft für Kardiologie – Herz und Kreislaufforschung
– Prof. Gunter Görge, Klinikum Saarbrücken, Medizinische Klinik II (1, 2) (DGK) (German Cardiac Society) (lead society) (1) – Dr. Jürgen Graf, Universitätsklinikum Marburg, Klinik für Anästhesie Deutsche Gesellschaft für Internistische Intensivmedizin und Notfall-
und Intensivtherapie (2) medizin (DGIIN) (German Society of Intensive Care and Emergency – Prof. Gerhard Hindricks, Universität Leipzig, Herzzentrum Leipzig, Klinik für Innere Medizin/Kardiologie, Abteilung für Rhythmologie (1) Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie
– Prof. Uwe Janssens, St. Antonius Hospital Eschweiler, Klinik für (DGTHG) (German Society for Thoracic and Cardiovascular Sur- Innere Medizin (1, 2) – Prof. Burkert Mathias Pieske, Medizinische Universität Graz, Universi - Österreichische Gesellschaft für Internistische und Allgemeine Inten-
tätsklinik für Innere Medizin, Klinische Abteilung für Kardiologie (1, 6) sivmedizin (ÖGIAIM) (Austrian Society of Internal and General Inten- – Dr. Roland Prondzinsky, Carl-von-Basedow-Klinikum Saalekreis sive Care Medicine) (4) GmbH, Bereich Merseburg, Klinik für Innere Medizin I (1) Deutsche Interdisziplinäre Vereinigung für Intensivmedizin (DIVI)
– Dr. Sebastian Reith, Universitätsklinikum Aachen, Medizinische (German Interdisciplinary Association of Intensive Care and Emer - gency Medicine) (5) – Dr. Martin Ruß, Universitätsklinikum Halle (Saale) der Martin- Österreichische Kardiologische Gesellschaft (ÖKG) (Austrian
Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik Society of Cardiology) (6) für Innere Medizin III (1, 2) (secretary) Deutsche Gesellschaft für Anästhesie und Intensivmedizin (DGAI)
– Dr. Dirk Schmitt, Universität Leipzig, Herzzentrum Leipzig, Klinik für (German Society of Anaesthesiology and Intensive Care Medicine) (7) Herzchirurgie (3) Deutsche Gesellschaft für Prävention und Rehabilitation (DGPR)
– Prof. Friedrich A Schöndube, Universitätsklinikum der Georg-August- (German Society of Preventive Medicine and Rehabilitation) (8) Universität Göttingen, Klinik für Thorax-, Herz- und Gefäßchirurgie (3*) – Prof. Gerhard Schuler, Universität Leipzig, Herzzentrum Leipzig, – Prof. Hans Anton Adams, Medizinische Hochschule Hannover, Klinik für Innere Medizin/Kardiologie (1) Stabsstelle Interdisziplinäre Notfall- und Katastrophenmedizin (5*) – Prof. Bernhard Schwaab, Klinik Höhenried, Abteilung Kardiologie (8*) – Prof. Christoph Bode, Universitätsklinikum Freiburg der Albert- – Prof. Rolf-Edgar Silber, Universitätsklinikum Halle (Saale) der Ludwigs-Universität Freiburg, Medizinische Universitätsklinik, Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Abteilung Innere Medizin III – Kardiologie und Angiologie (1) Poliklinik für Herz- und Thoraxchirurgie (3) – Prof. Josef Briegel, LMU Klinikum der Universität München, Klinik für – Prof. Ruth Strasser, Technische Universität Dresden, Medizinische Anaesthesiologie (7*) Fakultät "Carl Gustav Carus," Medizinische Klinik/Kardiologie (1) – Prof. Michael Buerke, Universitätsklinikum Halle (Saale) der Martin- – Prof. Ulrich Tebbe, Klinikum Lippe-Detmold, Klinik für Kardiologie Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik und Angiologie (1) für Innere Medizin III (1, 2*) – Prof. Hans-Joachim Trappe, Klinikum der Ruhr-Universität Bochum, – Dr. Arnd Christoph, Kliniken der Stadt Köln gGmbH, Krankenhaus Marienhospital Herne, Medizinische Klinik II (1, 2) Merheim, Medizinische Klinik II (1) – Prof. Karl Werdan, Universitätsklinikum Halle (Saale) der Martin- – Prof. Georg Delle-Karth, Universitäts-Kliniken des Allgemeinen Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik Krankenhauses Wien, Universitäts-Klinik für Innere Medizin II, für Innere Medizin III (1*, 2) (coordination) Klinische Abteilung für Kardiologie (6*) – Prof. Uwe Zeymer, Klinikum der Stadt Ludwigshafen, Medizinische – Prof. Lothar Engelmann, Universität Leipzig, Einheit für multidiszipli- näre Intensivmedizin des Universitätsklinikums (2) – Prof. Manfred Zehender, Universitätsklinikum Freiburg der Albert- – Prof. Raimund Erbel, Universitätsklinikum Essen, Westdeutsches Ludwigs-Universität Freiburg, Medizinische Universitätsklinik, Herzzentrum Essen, Klinik für Kardiologie (1) Abteilung Innere Medizin III – Kardiologie und Angiologie (1) – Dr. Markus Ferrari, Universitätsklinikum Jena, Klinik für Innere – Prof. Hans-Reinhard Zerkowski, Genolier Swiss Medical Network, Genolier (VD), Schweiz (3) – Prof. Hans-Reiner Figulla, Universitätsklinikum Jena, Klinik für – Prof. Bernhard Zwißler, LMU Klinikum der Universität München, Innere Medizin I (1) Klinik für Anaesthesiologie (7) – Dr. Ivar Friedrich, Universitätsklinikum Halle (Saale) der Martin- Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik Numbers in parentheses identify affiliation with a medical society.
für Herz- und Thoraxchirurgie (3) * Delegate of the relevant society with a vote in the nominal group – Dr. J. T. Fuhrmann, Technische Universität Dresden, Medizinische Fakultät "Carl Gustav Carus," Medizinische Klinik/Kardiologie (1) Addresses are those valid at the time the guideline was being – Dr. Alexander Geppert, KH Wilhelminenspital Wien, 3. Medizinische Abteilung, Kardiovaskuläre Intensivmedizin (4*, 6) Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 Concept and development of the guideline
The guideline was developed between 2004 and 2010
Recommendation grade and evidence levels
(see Leitlinienreport (guideline report) at www.leitli First, 16 sessions were held on the various sections of the guideline with those listed in Box 1 from Strongly recommended: "shall" (usually based on studies with evidence the medical societies as shown. Next, a multipart nom-inal group process—with Prof. I. Kopp (AWMF) in the Recommended: "should" (usually based on studies with evidence level 2++ chair—was carried out from 19 August 2008 to 25 Sep-tember 2009, in which each medical society had one No recommendation: "may" (no confirmed study results exist that demon- strate either a beneficial or a harmful effect) vote. The recommendations were agreed in consensus. Recommendations on which there was no consensus Rejected: "should not" (negative recommendation) are inidicated accordingly and the different interpre- Strongly rejected: "shall not" (strong negative recommendation) tations of the evidence laid out (Table 1). Before publi- cation, the draft guideline was made available to other High-quality systematic reviews of randomized controlled trials (RCTs) or medical societies from October to December 2009 on RCTs with a very low risk of bias the home page of the AWMF, the German Cardiac Well performed systematic reviews of RCTs or RCTs with a low risk of bias Society (Deutsche Gesellschaft für Kardiologie – Herz- und Kreislaufforschung), and other medical societies High-quality systematic reviews of case-control or cohort studies with very low risk of confounders or bias and a high probability of causal relationships for discussion (consultation phase). Comments were forwarded to the expert groups for their opinion and Well performed systematic reviews of case-control or cohort studies with a low risk of confounders or bias and a moderate risk of noncausal relation- discussion as to whether any changes were needed (see Leitlinienreport at In the event no Nonanalytic studies changes were made, but important comments were added as footnotes. All members agreed that there Consensus opinion of experts based on studies and clinical experience or in the interests of patients' safety (e.g., monitoring) would be no patient participation (see Leitlinienreport at
In accordance with the AWMF recommendation for recommendation grading, the recommendation and The guideline is valid until next revised or until grading system of this S3 guideline follows the pattern of the National Care Guideline "Chronic CHD" (www.
January 2014 at the latest., which follows the Scottish Intercollegiate Guidelines Network for the grading of evidence ( The S3 guideline "Infarktbedingter kardiogener Schock: Diagnose, Monitoring und Therapie" (Infarc-tion-Related Cardiogenic Shock: Diagnosis, Monitor-ing, and Treatment) was developed under conditions of editorial independence; coordination and logistic support were financed by the German Cardiac Society. Travel costs were borne by the medical societies, and the expert work was done on a voluntary basis without the payment of any fees. All the members of the guide-line development group have declared any conflicts of Contents of the German–Austrian S3 guideline
interest relating to the development of the S3 guideline; "Infarction-related cardiogenic shock: diagnosis,
the list forms part of the guideline report at www.leitli monitoring, and treatment"
The aims of the guideline and who the guideline is for
The aim of the S3 guideline "Infarktbedingter kardio-gener Schock: Diagnose, Monitoring und Therapie" (Infarction-Related Cardiogenic Shock: Diagnosis, Diagnosis, monitoring, and treatment of infarction-related cardiogenic shock Monitoring, and Treatment) is to improve the quality of Definition, diagnosis, and monitoring
care of patients with ICS, by publishing evidence-based Earliest possible coronary revascularization
recommendations. It also presents the "state of the art" in diagnostics, monitoring, and treatment, thus repre- Cardiovascular support
senting a starting point for comparative studies. This is Treatment of complications of infarction-related cardiogenic shock
particularly to be emphasized, because many of the rec-ommendations in this S3 guideline are based on expert Supportive therapy for multiorgan dysfunction syndrome (MODS)
opinions because of the lack of high-quality evidence.
Nutrition and insulin therapy, red cell substitution and prophylaxis,
The recommendations in the S3 guideline are considerations regarding limitation of treatment directed at physicians managing patients with shock Aftercare and rehabilitation
and acute myocardial infarction: that is, in particular, cardiologists and specialists in internal medicine, inten- sivists, heart surgeons, anesthetists, physicians working Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 in interdisciplinary emergency admission services, emergency physicians, and rehabilitation specialists, along with the care staff working with them.
Data acquisition and evaluation of recommendations and
A systematic search was conducted of international
If not already given: 1 × 250 to 500 mg acetylsalicylic acid i.v., then 100 mg/day
guidelines in order to produce a statement of the the -matic areas and questions on which there was consen-sus ("source guidelines"; see Leitlinienreport at www.
Unfractionated heparin: bolus 60 U/kg, max. 4000 to 5000 U, In addition, a primary systematic litera- then continuous infusion, target PTT 50 to 70 s/ACT >150 s
ture search was carried out (PubMed: search terms (ab-stracts) "myocardial infarction and cardiogenic shock") (Figure 3) of publications from 1 January 1990 to 30 Coronary
Possibility of
Early phase of ICS,
September 2009 (3546 results). Evidence tables were symptoms <3 h
produced for the themes "Revascularization" and and treatment
"IABP implantation." within 90 min?
Can lesion be
The evidence in the study data and the assigning of approached
recommendation grades was done in the above- mentioned nominal group process in accordance with pathology
the recommendation grades and evidence levels listed (high-grade
in Table 1.
The contents list of the guideline is reproduced in Box 2; a selection of the recommendations is given in GP IIb/IIIa
eTable 1. Recommendations that particularly deserve discussion will be presented in more detail in the Transport to a
hospital with

present article (Box 3).
a cardiac cath lab
Diagnosis and monitoring: initial phase
Case by case decision:
A preliminary diagnosis of "infarction-related cardio- then 75 mg/day
genic shock" (ICS) (E 1/2 in eTable 1) usually has to be immediately
made quickly by the emergency physician during the  stabilization prehospital phase on the basis of the 12-lead ECG   ("STEMI," ST-segment elevation myocardial infarc- after stabilization
tion) and clinical findings ("cardiogenic shock") (rec- PCI (stent
ommendation ↑↑). Even in the rare case of ICS follow- ing NSTEMI (no ST elevation on the ECG), the phys- ician can diagnose ICS on the basis of clinical criteria target vessel
in a patient with ACS.
The most important—though not ubiquitous—symp- tom of ICS is hypotension <90 mm Hg systolic for at Successful
Any other
least 30 minutes, associated with signs of reduced organ perfusion. Invasive measurement of cardiac out- relevant
put (e.g., cardiac index < 2.2 L × min-1 × m-2 and PAOP > 15 mm Hg) (3) is not necessary for a diagnosis of Operative
ICS. However, one patient in four with ICS presents without initial hypotension; in such cases, the diagnosis must rest on clinical signs of reduced organ perfusion Revascularization is the most important element of treatment of ICS.
(cold extremities, oliguria, altered mental status, e.g., *1 After initial stabilization/before cardiac catheter investigation; *2 Persistent shock after revascularization;*3 Currently there is not enough evidence for the use of IABP in PCI or ACB; in patients who have received fibrinolytic treatment, the IABP should be used Revascularization of the infarcted coronary artery (Figure 1) is performed as early as possible, usually by PCI (↑↑, E13 in eTable 1). Initial cardiovascular and re-spiratory stabilization of the PCS patient—dobutamine/norepinephrine, ventilation for those with respiratory failure, adequate volume replacement for those with Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 right ventricular infarction—is necessary so that the coronary intervention may be carried out safely and efficiently.
The superiority of the principle of earliest possible Hemodynamic shock therapy
coronary revascularization has been evident since the Hemodynamic monitoring CO/CI, MAP, CPI
SHOCK trial (3, 7). Early reperfusion of the coronary arteries is an important predictor of long-term survival (2) (eTable 2); when this is achieved, 132 MAP >65 and <75 mm Hg
lives can be saved for every 1000 shock patients treated (7).
PCI on the coronary infarct artery usually takes the form of stent implantation (↑, E 14 in eTable 1) with in-tensive use of platelet aggregation inhibitors. If inter- >75 mm Hg
<65 mm Hg
ventional revascularization is unsuccessful, surgery should be carried out as rapidly as possible. If several significant coronary stenoses are present, decisions Increase
may in some cases have to be made about further inter- norepinephrine, norepinephrine,
ventional or surgical revascularization.
Resuscitated patients form a special subgroup, which may make up as much as 30% of all patients with ICS >800 to 1000
<800 to 1000
(8, 9). Early PCI should be considered in rapidly defi- brillated patients (↑, E 78 in eTable 1) and mild hypo-thermia (32° to 34°C) induced for 12 to 24 hours (↑, E 79/80 in eTable 1). Regular re-evaluation
800 to 1000
of treatment goals;
dyn × s × cm-5
be particularly aware
Persistent shock after revascularization
of renewed volume
The goals of hemodynamic management if shock requirement after
symptoms persist are blood pressure stabilization and decrease in afterload
(monitoring by
measure CO
ensuring adequate organ perfusion (↑, E 32/33 in eTable 1; Figure 2). To achieve this goal with adequate preloading and the least possible use of catechola-mines, close invasive monitoring including repetitive CI >2.5 L × min-1 × m-2
invasive measurement of cardiac output (↑↑, E 12) is necessary (Figure 2). As to perfusion pressure, a mean arterial pressure between 65 and 75 mm Hg and cardiac index (cardiac output related to body surface area) of >2.5 L × min-1 × m-2 should be aimed at; as blood flow No change
equivalents, a SVR of 800 to 1000 dyn × s × cm-5, a simendan
vO2 >65%, or the cardiac power (product of cardiac output and mean arterial pressure as a measure of over-all cardiac hydraulic performance) or cardiac power index (CP > 0.6 W or CPI > 0.4 W × m-2) (10–13) may be chosen instead of cardiac index (Figure 2).
Target parameters of medical therapy:
MAP 65 to 75 mm Hg with SVR 800 to 1000 dyn × s × cm-5 or
Which vasopressor and which inotrope?
MAP 65 to 75 mm Hg with CI >2.5 L × min-1 × m-2 or
MAP 65 to 75 mm Hg with S O >65% or
Norepinephrine is the vasopressor of choice in patients CP >0.6 W (CPI >0.4 W/m2)*4
with MAP values below 65 mm Hg (↑, Figure 2; E 34 with in all cases minimal use of catecholamines, heart rate <110/min,
to E 38 in eTable 1). The MAP can usually be effec- and improvement in the clinical
tively raised by intravenous infusion of 0.1 to 1 μg × signs of cardiogenic shock
kg-1 × min-1. In the SOAP II study of 1679 patients with
shock of various etiologies (14), norepinephrine Hemodynamic shock therapy: Hemodynamic shock therapy focuses on achieving
showed a tendency to lower mortality than dopamine adequate organ perfusion using the minimum of catecholamines.
(28-day mortality 45.9% vs. 50.2%; odds ratio [OR] *1 Shock after revascularization;
1.19; confidence interval [CI] 0.98 to 1.44; p = 0.07) *2 Treatment of MODS;
and significantly fewer arrhythmias (12.4% vs. 24.1%),
*3 In patients with raised SVR, norepinephrine treatment is always ended before treatment especially atrial fibrillation. In the prospectively de- with nitrates or sodium nitroprusside is started. ÖKG and ÖGIAIM (see Box 1) prefer treat-ment with nitroglycerine rather than sodium nitroprusside in patients with raised SVR, fined subgroup of patients with cardiogenic shock, the even though catecholamine treatment has been stopped.
norepinephrine treatment led to a significantly better *4 CP > 0.6 W corresponds to a cardiac output of 5 L/min with an MAP of 65 mm Hg and SVR survival rate than the dopamine treatment (OR 0.75; p of 880 dyn × s × cm-5 = 0.03; [14]).
Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 These sobering results of the randomized controlled IABP SHOCK trial (18) are confirmed by the negative results of a Cochrane analysis of six randomized What is new in comparison to the
studies of a total of 190 ICS patients (19) and a meta- established guidelines?
analysis of 10 529 ICS patients from nine cohort studies (20). The ICS patients treated with PCI (the Pressure monitoring is not enough for hemodynamic
recommended standard therapy) derived no benefit treatment after revascularisation! Additional cardiac from adjunctive IABP treatment; rather, they even output monitoring is mandatory.
showed an absolute increase in mortality of 6% (ARR Dobutamine is the inotropic agent of choice; norepi-
+6%; RRR +15%) (20); only when used together with nephrine is the vasopressor of choice; levosimendan systemic fibrinolysis did adjunctive IABP lead to an can be used in addition in patients with catecholamine- 18% reduction in mortality (ARR –18%; RRR –26%) refractory shock.
(20). It is to be hoped that the currently ongoing pros- Even in resuscitated patients, earliest possible PCI
pective multicenter IABP SHOCK II study (26) will should be considered on a case by case basis.
elucidate whether the adjunctive use of IABP in PCI-treated ICS patients can reduce mortality. Even weaker Intra-aortic balloon counterpulsation (IABP) has been
is a "may" recommendation in selected cases for the use of mechanical cardiac support systems, which, If ventilation is needed, it should be invasive and
principally in animal experiments, have proved able to lung-protective.
improve hemodynamics, reduce wall tension, and im-prove coronary flow reserve. However, large clinical user studies are currently under way and are expected to produce greater clarity on this point in the near future (21).
Dobutamine is the inotrope of choice (↑, Figure 2; For this reason, the German–Austrian S3 guideline E 34 to E 38 in eTable 1). In the dose range of 2.5 to 10 gives (E 44 to E 47 in eTable 1) only a weak recom- μg × kg-1 × min-1 there is a dose–effect relationship. In mendation (↑, E 44) for the use of IABP in ICS patients
a multicenter cohort observation study of 1058 shock treated with systemic fibrinolysis, and only "may"
patients treated with catecholamines (15), application information for patients treated with PCI (↔, E 45).
of dopamine was an independent risk factor for mortal-
ity, while application of dobutamine or norpinephrine Ventilation
was not.
Mechanical ventilation of an ICS patient ensures In ICS refractory to catecholamine treatment, current oxygenation and relieves the heart of the work of research results support the additional use of levosi- breathing. In contrast to the recommendation for non - mendan (loading dose 12 to 24 μg × kg-1 over 10 min- invasive ventilation in patients with decompensated utes, followed by 0.05 to 0.2 μg × kg-1 × min-1) more heart failure, in patients with ICS invasive ventilation than that of phosphodiesterase III inhibitors such as should be preferred (↑, eFigure; E 86 in eTable 1). The enoximone or milrinone (↑, Figure 2; E 34 to E 38 in reasons for this are the constant, stable ventilation eTable 1) (16). Patients with coronary heart disease conditions provided by invasive ventilation and the with decompensated heart failure who have previously avoidance of psychomotor excitement that would ex-been treated with beta-blockers will have more hemo - haust the patient. Although hemodynamic stability is dynamic benefit from a phosphodiesterase III inhibitor the main focus initially, the advantages of lung-than from dobutamine (17).
protective ventilation should be made use of at the ear-liest possible moment (↑, E 88 in eTable 1), although Skepticism about intraortic balloon counterpulsation
the available data in this regard, especially in ICS Both the European and the American myocardial in- patients, are very sparse (22). The depth of analgesia/ farction guidelines regard the use of IABP as a class I sedation should be recorded three times a day using the recommendation. The favorable hemodynamic effect Richmond Agitation–Sedation scale (↑, E 93 in eTable of IABP is ascribed to an increase in diastolic coronary 1). Weaning, which is often difficult in ICS patients, perfusion with a simultaneous decrease in the afterload. should follow a weaning protocol (↑, E 94 in eTable 1), In ICS patients, however, the hemodynamic effects of and before weaning starts, the following conditions IABP are moderate (18): Although IABP can relieve should be fulfilled: hemodynamic stability, absence of the left ventricle—as is seen by lower BNP concen- myocardial ischemia, and absence or regression of in- trations—the cardiac index is not significantly im- flammation or infection.
proved in the first few days after the onset of shock.
Even more importantly, neither MODS (measured as Intensive care
the APACHE II score), which determines the progno-
The initially favorable results of continuous sis, nor the systemic inflammation (measured as the intravenous insulin therapy with the aim of achieving serum IL-6 concentration) is improved by the IABP normoglycemia in intensive care patients were not treatment (18).
confirmed in later studies such as the NICE-SUGAR Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 study (23). In view of these results and of the fact that high blood glucose levels are unfavorable prognostic indicators in heart attack patients (24), a "middle way" Database search
is recommended in ICS patients, aiming to keep blood (myocardial [AND] cardiogenic shock
glucose values below 150 mg × dL-1/< 8.3 mmol × L-1 (↑, eFigure; E 99 in eTable 1).
The use of insulin–glucose–potassium infusions, for 3546 results (abstracts)
which there have been convincing experimental results, has not proved effective in clinical studies of patients after myocardial infarction (24) and should therefore Quantitative literature analysis
not be used in ICS patients either (↓↓, E 100 in eTable 1).
Approx. 6000 relevant publications
At what Hb threshold value should intensive care patients receive red cell concentrates? There is contro-versy about this, especially in regard to intensive care Qualitative literature analysis
patients with cardiac disease and older patients in whom increased oxygen requirement of the underper- Approx. 457 cited publications
fused heart may be assumed. Given the available data, in ICS patients red cell concentrates should be given from a Hb value < 7.0 g × dL-1/<4.3 mmol × L-1 or 35 guidelines and consensus documents from
hematocrit < 25%. Target values are Hb 7.0 to 9.0 g × medical societies
dL-1/4.3 to 5.6 mmol × L-1 or hematocrit 25% (↑, E 16 systematic reviews/meta-analyses
95 randomized studies
101), or, in older patients (>75 years), 30% (↑, E 101 in 197 cohort studies/case-control studies
eTable 1).
10 case series/case reports
Mandatory measures in ICS patients are thrombosis 104 other (comments, book contributions, reviews,
expert opinions, etc.)
prophylaxis—by means of intravenous administration of heparin—and stress ulcer prophylaxis.
Literature search and selection of relevant publications
Recommendations for aftercare/rehabilitation
Once the ICS patient has survived the shock, particular
attention must be paid to risk stratification in the
post-intensive-care phase. The current rehabilitation guidelines list both acute STEMI/NSTEMI and decom-pensated heart failure as class I/A indications for car-diological rehabilitation. In patients with ICS, inpatient rehabilitation lasting usually about 3 to 4 weeks should be aimed at if possible, because of the severity of the infarction event.
The most effective treatment measure for reducing
mortality among ICS patients is revascularization of the
infarct vessel as early as possible (eTable 2). Despite
successful revascularization, almost one in two ICS pa-
tients still dies. This is due to the sequelae of protracted
shock: the severe systemic inflammatory reaction
(SIRS) and the multiorgan dysfunction syndrome
(MODS) (18). Consequently, any further progress can
only be achieved through effective anti-SIRS (25),
anti-MODS, and general intensive care medical treatment, which hitherto have not received enough attention in ICS. Above all, comparison with the available evidence-based recommendations for the treatment of severe sepsis and septic shock shows the deficits in, for example, lung-protective ventilation and weaning, and in the standardized early hemodynamic stabilization. These aspects emphasize intensive care medicine approaches to the treatment of ICS, rather than cardiological approaches, and the present German-Austrian guideline takes more account of them than do Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 the European and American myocardial infarction ACB aorto-coronary Weaknesses and limitations of the guideline
acute coronary syndrome High-quality randomized controlled studies and meta- absolute risk reduction analyses relating to the diagnosis, monitoring, and Arbeitsgemeinschaft der Wissenschaftlichen treatment of ICS are available only for a few aspects, so Medizinischen Fachgesellschaften (Associa - that the guideline recommendations very often have to tion of Scientific Medical Societies in Germany) rely on expert opinions. So far, recommendations about nursing have been entirely omitted, both in terms of the B-type natriuretic peptide catheter lab and the intensive care unit, since the work begun on the nursing aspects has not yet been brought to the desired conclusion. It is to be hoped that this guideline, which shows how little evidence there is on cardiac power/cardiac power index some points, will encourage the carrying out of high- Deutsche Gesellschaft für Kardiologie – Herz- quality studies. und Kreislaufforschung (German Cardiac The authors thank all participants, all the medical societies involved, and the AWMF (Box 1), who have contributed to the development of this guideline.
GP IIb/IIIa, glycoprotein IIb/IIIa intra-aortic balloon pump Conflict of interest statement
K. Werdan has received lecture fees from Baxter, Datascope, Maquet, and
infraction-related cardiogenic shock Orion, has held a position on the Advisory Boards of Baxter and Datascope, and has received research funding from Datascope.
G. Delle-Karth has received consultancy fees from Orion, Abbott, Bayer AG, mean arterial pressure and St Jude Medical and lecture fees from Orion, Abbott, Biotronik, Daiichi Sankyo, and Eli Lilly. He has received reimbursement of travel or conference costs from Medtronic, Biosensors, Abbott, Boston Scientific, Daiichi Sankyo, Eli Lilly, and Orion. He has received funding for research projects from Medtronic, multiorgan dysfunction syndrome Abbott, Boston Scientific, Braun, Siemens, GE Healthcare, and Biosensors.
A. Geppert has received reimbursement of travel and event costs from Med- tronic, Abbott, and Orion Pharma, and has received lecture fees from Orion Pharma and Medtronic.
NSTEMI non-ST-segment elevation myocardial infarction M. Ruß and F.A. Schöndube declare that no conflict of interest exists.
pulmonary artery occlusion pressure M. Buerke has received lecture fees from Orion Pharma, Datascope, and Abbott.
percutaneous coronary intervention Manuscript received on 22 December 2011, revised version accepted on relative risk reduktion 24 February 2012.
ST-segment elevation myocardial infarction Translated from the original German by Kersti Wagstaff, MA.
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ventricular septal defect 2. Hochman JS, Sleeper LA, Webb JG, et al.: Early revasculariz- Weaning gradual reduction of ventilatory support and ation and long-term survival in cardiogenic shock complicating intensive medical care acute myocardial infarction. JAMA 2006; 295: 2511–5.
3. Hochman JS, Sleeper LA, Webb JG, et al.: Early revasculari - zation 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: 625–34.
4. Kohsaka S, Menon V, Lowe AM, et al.: Systemic inflammatory response syndrome after acute myocardial infarction compli-cated by cardiogenic shock. Arch Intern Med 2005; 165: 1643–50.
5. 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 Euro-pean Society of Cardiology. Eur Heart J. 2008; 29: 2909–45.
6. Werdan K, Ruß M, Buerke M, et al.: Deutsch-österreichische S3-Leitlinie Infarktbedingter kardiogener Schock. Diagnose, Monitoring und Therapie. Der Kardiologe 2011; 5: 166–224; In-tensivmed 2011; 48: 291–344; Intensiv- und Notfallbehandlung 2011; 36: 49–130.
Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 7. Hochman JS, Sleeper LA, White HD, et al.: One-year survival IABP SHOCK Trial for attenuation of multiorgan dysfunction following early revascularization for cardiogenic shock. Jama syndrome. Crit Care Med 2010; 38: 152–60.
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19. Unverzagt S, Machemer MT, Solms A, et al.: Intra-aortic balloon 8. Arntz HR, Bossaert LL, Danchin N, Nikolaou NI: European Resus- pump counterpulsation (IABP) for myocardial infarction compli- citation Council Guidelines for Resuscitation 2010 Section 5. cated by cardiogenic shock. Cochrane Database Syst Rev 2011; Initial management of acute coronary syndromes. Resuscitation 2010; 81: 1353–63.
20. Sjauw KD, Engstrom AE, Vis MM, et al.: A systematic review and 9. Nolan JP, Soar J: Postresuscitation care: entering a new era. meta-analysis of intra-aortic balloon pump therapy in ST-eleva - Curr Opin Crit Care 2010; 16: 216–22.
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power and systemic vascular resistance in the pathophysiology 21. Cyrus T, Mathews SJ, Lasala JM: Use of mechanical assist and diagnosis of patients with acute congestive heart failure. during high-risk PCI and STEMI with cardiogenic shock. Catheter European Journal of Heart Failure 2003; 5: 443–51. Cardiovasc Interv 2010; 75(Suppl 1): 1–6.
11. Fincke R, Hochman JS, Lowe AM et al.: Cardiac power is the 22. Kouraki K, Schneider S, Uebis R, et al.: Characteristics and clini- strongest hemodynamic correlate of mortality in cardiogenic cal outcome of 458 patients with acute myocardial infarction shock: A report from the SHOCK trial registry. Journal of the requiring mechanical ventilation. Results of the BEAT registry of American College of Cardiology 2004; 44: 340–8.
the ALKK-study group. Clin Res Cardiol 2011; 100: 235–9.
12. Mendoza DD, Cooper HA, Panza JA: Cardiac power output pre- 23. Finfer S, Chittock DR, Su SY, et al.: Intensive versus conven- dicts mortality across a broad spectrum of patients with acute tional glucose control in critically ill patients. N Engl J Med cardiac disease. Am Heart J 2007; 153: 366–70.
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13. Russ MA, Prondzinsky R, Carter JM, et al.: Right ventricular 24. Cobb LA, Killip T, Lambrew CT, et al.: Glucose-insulin-potassium function in myocardial infarction complicated by cardiogenic infusion and mortality in the CREATE-ECLA trial. Jama 2005; shock: Improvement with levosimendan. Crit Care Med 2009; 293: 2597; Letters and authors' reply: 2005; 293: 2596–7.
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25. The Triumph-Investigators: Effect of tilarginine acetate in pa- 14. De Backer D, Biston P, Devriendt J, et al.: Comparison of Dopa- tients with acute myocardial infarction and cardiogenic shock: mine and Norepinephrine in the treatment of shock. N Engl J the TRIUMPH randomized controlled trial. Jama 2007; 297: Med 2010; 362: 779–89.
15. Sakr Y, Reinhart K, Vincent JL, et al.: Does dopamine adminis- 26. Thiele H, Schuler G, Neumann FJ, et al. on behalf of the IABP- tration in shock influence outcome? Results of the Sepsis Shock II Trial Investigators: Intraaortic balloon counterpulsation Occurrence in Acutely Ill Patients (SOAP) Study. Crit Care Med in myocardial infarction complicated by cardiogenic shock: De- 2006; 34: 589–97.
sign and rational of the intraaortic balloon pump in cardiogenic 16. Fuhrmann JT, Schmeisser A, Schulze MR, et al.: Levosimendan shock II trial (IABP-SHOCK II). Am Heart J, 2012, in press.
is superior to enoximone in refractory cardiogenic shock compli-cating acute myocardial infarction. Crit Care Med 2008; 36: Corresponding author
Prof. Dr. med. Karl Werdan 17. Metra M, Nodari S, D'Aloia A, et al. Beta-blocker therapy in- Universitätsklinik und Poliklinik für Innere Medizin III fluences the hemodynamic response to inotropic agents in Universitätsklinikum Halle (Saale) Ernst-Grube-Str. 40 patients with heart failure: A randomized comparison of dobuta- 06120 Halle (Saale), Germany mine and enoximone before and after chronic treatment with metoprolol or carvedilol. Journal of the American College of Cardiology 2002; 40: 1248–58.
18. Prondzinsky R, Lemm H, Swyter M, et al.: Intra-aortic balloon counterpulsation in patients with acute myocardial infarction @ eTables and eFigure: complicated by cardiogenic shock: the prospective, randomized Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19): 343–51 A selection of recommendations of the German-Austrian S3 guideline "Infarktbedingter kardiogener Schock: Diagnose,
Monitoring und Therapie" (Infarction-Related Cardiogenic Shock: Diagnosis, Monitoring, and Treatment)
Diagnosis and monitoring
Act fast! Diagnosis and treatment should be carried out immediately and simultaneously. The diagnosis
of infarction-related cardiogenic shock is based on clinical assessment (signs of underperfusion of or- gans) and on noninvasive hemodynamic measurements (e.g., after exclusion of hypovolemia: RRsyst <90 mm Hg for at least 30 min) Cardiovascular management should be guided by hemodynamic perfusion pressure ranges (e.g.,
mean arterial pressure 65 to 75 mm Hg and cardiac index >2.5 L × min-1 × m-2 or SVR 800 to 1000 dyn × s × cm-5 or SvO2/ScvO2 >65% or cardiac power (CP)/cardiac power index (CPI) >0.6 W/> 0.4 W × m-2) Coronary revascularization as early as possible!
The infarct vessel should be revascularized as soon as possible, usually by means of PCI, in patients in the initial phase of shock within 2 hours from first contact with a physician, otherwise as early as possible Intracoronary stenting should be preferred Inotropic drugs and vasopressors in patients with systolic pump failure
Dobutamine should be given as an inotropic drug (↑) and norepinephrine as a vasopressor (↑). In
cases of catecholamine-refractory cardiogenic shock, levosimendan or phosphodiesterase-III
inhibitors should be used (↔), with levosimendan being preferred (↑)
Intra-aortic balloon counterpulsation (IABP) in patients with systolic pump failure
In patients undergoing fibrinolysis treatment, IABP should be carried out adjunctively In patients undergoing PCI, IABP may be considered, but the available evidence is unclear Patients with infarction-related cardiogenic shock who have survived cardiac arrest
In resuscitated patients whose cardiac arrest was rapidly reversed by defibrillation, earliest possible
PCI should be considered on a case by case basis, since this is expected to improve the prognosis.
Mild hypothermia (32°C to 34°C) for 12 to 24 hours should be induced in comatose patients after
cardiopulmonary resuscitation, both after resuscitation because of ventricular fibrillation (E 79) and
because of asystole and also after cardiac arrest in hospital (E 80)
Pulmonary dysfunction: respiratory support, ventilation, analgosedation, and weaning
Patients with backward failure should be invasively ventilated
Invasive ventilation should be preferred to noninvasive ventilation
If ventilation is still indicated after hemodynamic stabilization, lung-protective ventilation should be
given (VT ≤ 6 mL × kg-1; peak pressure ≤ 30 mbar) Analgosedation should be consistently measured and recorded using a sedation scale
Weaning should always follow a standardized established weaning protocol
Supportive treatment of multiorgan dysfunction syndrome (MODS) and general intensive care measures including prophylaxis
Blood glucose levels should be kept <150 mg × dL-1/< 8.3 mmol × L-1 by means of insulin
Glucose-insulin-potassium infusions should not be given
Red cell concentrate transfusions should be given when hemoglobin values are <7.0 g × dL-1 /4.3 mmol
× L-1 or hematocrit <25% and the values be brought up to 7.0 to 9.0 g × dL-1/4.3 to 5.6 mmol × L-1 or ↑↑ / ↓↓ strongly recommended ("shall/shall not"); ↑ recommended ("should"); ↔ no evidence-based recommendation possible. The numbering refers to the print version of the guideline (6) Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19) Werdan et al.: eTables Results of the SHOCK study: 30-day to 6-year survival rates of the two groups
revasculari zation
Survival: 30 days Survival: 6 months Survival: 12 months Survival: 6 years Data assembled from (1, 4, 5) Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19) Werdan et al.: eTables Ventilation and treatment
of MODS:
*1 Hemodynamic shock
Ventilation and MODS
*2 In the sepsis guidelines, it Treatment of MODS
is recommended to posi-tion the upper body at an angle of 45° Is ventilation indicated?
*3 ÖGIAIM (see Box 1) rec- ommends a blood glu-cose range of 80 to 120 Physical exhaustion
Blood glucose >150 mg/dL*3
mg/dL (4.4 to 6.7 with altered mental status?
*4 RASS: Richmond Agi- tation–Sedation Scale; *5 CAM-ICU (Confusion Assessment Method for Intensive Care Units): test to evaluate delirium in the High respiratory work
CRRT*6 or daily
intensive care unit; (AF, accessory muscles?)
*6 CRRT: continuous renal replacement therapy Hypoxia despite
Bring blood sugar
10 L/min O ?
<150 mg/dL
daily/every 6 h
Assisted breathing
Therapeutic goals for respiration/ventilation:
via nasal tube
pO > 10.6 kPa/80 mm Hg
pH >7.2 (>7.15 if cardiovascular
stability unchanged), FiO <0.65
Does the patient
feel comfortable;
are pain, agitation,
TV max. 6 mL/kg BW
and delirium
max. 30 mbar
(if cardiac function allows)
Daily monitoring
of targets:
the patient
Upper body raised*2
optimization of
by 10% to 25% daily
Continue assisted
Fentanyl 0.8 to
Set target for
3.5 mg/kg BW/h
Pain scale
0.7 (1.0) mg/kg BW/h

Acute: midazolam
Assessment of
Set target
every 15 min
for sedation
Long-term sedation:
Midazolam 0.01 to
0.18 mg/kg BW/h
Set target
Haloperidol 2.5 to 5 mg
for treatment
every 10 to 20 min,
of delirium
of delirium
25% of the dose
as maintenance dose
Deutsches Ärzteblatt International Dtsch Arztebl Int 2012; 109(19) Werdan et al.: eFigure



JNM J Neurogastroenterol Motil, Vol. 21 No. 3 July, 2015 pISSN: 2093-0879 eISSN: 2093-0887 Journal of Neurogastroenterology and Motility Distribution of 5-HT3, 5-HT4, and 5-HT7 Receptors Along the Human Colon Nor S Yaakob,1,2 Kenneth A Chinkwo,1,3 Navinisha Chetty,1 Ian M Coupar,1 and Helen R Irving1* 1Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville Victoria, Australia;

03 tiger report

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