[Short version of the 2nd edition of the German-Austrian S3 guidelines "Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment"]. / Kurzversion der 2. Auflage der deutsch-österreichischen S3-Leitlinie "Infarkt-bedingter Kardiogener Schock ­ Diagnose, Monitoring und Therapie".

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.

[Therapy of cardiogenic shock : A success story of German cardiology]. / Therapie des kardiogenen Schocks : Eine Erfolgsgeschichte der deutschen Kardiologie.

In contrast to the situation in the 1960s and 1970s, the mortality risk for patients with myocardial infarction has been clearly reduced, particularly for those with myocardial infarction with cardiogenic shock (MICS). Approximately 5­10 % of patients with a myocardial infarction are affected by a MICS and the mortality risk is between 30 % and 50 %. The primary percutaneous coronary intervention with stent implantation should be carried out as quickly as possible in order to reduce the mortality to around 20 %. This article gives an overview of the currently available options for conservative and fibrinolytic treatment of MICS, of the interventional treatment of cardiogenic shock in the era of intravenous and intracoronary infarct treatment as well as without thrombolysis. In addition, the currently available mechanical support systems and the possibilities for surveillance and monitoring of patients are presented.

[Use of vasopressors and inotropics in cardiogenic shock]. / Einsatz von Vasopressoren und Inotropika im kardiogenen Schock.

Vasoactive drugs and inotropic agents are important for the hemodynamic management of cardiogenic shock. In this article the use of different vasoactive and ionotropic drugs in cardiogenic shock is presented. Hemodynamic management during cardiogenic shock occurs after initial moderate volume delivery by dobutamine to increase inotropism. If adequate perfusion pressures are not achieved norepinephrine is administered. If a sufficient increase in cardiac performance can still not be achieved by the treatment, administration of levosimendan or phosphodiesterase (PDE) inhibitors may be necessary. Levosimendan is superior to PDE inhibitors for patients in cardiogenic shock. The aim of hemodynamic management in cardiogenic shock is to allow the transient use of inotropics and vasopressors in the lowest necessary dose and only as long as necessary. The daily question is whether the dose can be reduced or in the case of deterioration whether the use of an extracorporeal circulatory support system should be considered. There are currently no available data on mortality that demonstrate the benefit of hemodynamic monitoring using target criteria. The advantage, however, results from the economic use of inotropics and vasopressors by certain target criteria.

[Modern drug therapy in cardiovascular intensive care medicine]. / Moderne Arzneitherapie in der kardiovaskulären Intensivmedizin.

Vasoactive drugs and inotropes are important in the hemodynamic management of patients with cardiogenic shock despite modest volume administration. Currently, the concept of cardiac relief is pursued in the treatment of acute heart failure. In this article we present the use of different drugs in the intensive care unit for acute heart failure and cardiogenic shock. In acute heart failure catecholamines are only used during the transition from heart failure to cardiogenic shock. Here, the therapeutic concept of ventricular unloading is more sought after. This can be achieved by the use of diuretics, nitrates, levosimendan (inodilatator), or in the future serelaxin. The hemodynamic management in cardiogenic shock occurs after moderate volume administration with dobutamine to increase inotropy. If no adequate perfusion pressures are achieved, norepinephrine can be administered as a vasopressor. If there is still no sufficient increase in cardiac output, the inodilatator levosimendan can be used. Levosimendan instead of phosphodiesterase inhibitors in this case is preferable. The maxim of hemodynamic management in cardiogenic shock is the transient use of inotropes and vasopressors in the lowest dose possible and only for as long as necessary. This means that one should continuously check whether the dose can be reduced. There are no mortality data demonstrating the utility of hemodynamic monitoring based on objective criteria­but it makes sense to use inotropes and vasopressors sparingly.

Are the elderly different? Factors influencing mortality after percutaneous coronary intervention with stent implantation.

BACKGROUND: The aim of this study was to investigate factors influencing mortality after percutaneous coronary intervention (PCI) in patients aged ≥ 75 years compared to younger patients. PATIENTS AND METHODS: A total of 1,809 coronary heart disease (CHD) patients after PCI with stent implantation in our hospital were assessed. Kaplan-Meier analyses with log-rank test and Cox regression analyses were performed on three predefined models concerning primary endpoint of all-cause mortality. Model 1 was a univariate analysis of the influence of age dichotomized by age 75 years on the primary endpoint. Model 2 included age and classical cardiovascular risk factors (CVRFs, e.g., body mass index (BMI), smoking, diabetes, and hypertension). Model 3 consisted of age, classical CVRFs, and additional factors (e.g., medication; hemoglobin, peripheral arterial disease (PAD), low-density lipoprotein cholesterol (LDL-C) and creatinine levels, and left ventricular ejection fraction (LVEF)). RESULTS: In the mean follow-up of 137 ± 61 weeks 375 patients died. Age ≥ 75 years was significantly related to mortality in all models. In model 3, previous stroke, PAD, diabetes, elevated levels of serum creatinine, and increased LDL-C were related to elevated mortality, higher hemoglobin levels, and LVEF > 50% were associated with decreased mortality in all patients and in patients < 75 years. In patients ≥ 75 years arterial hypertension was associated with poor outcome (hazard ratio (HR) 7.989, p = 0.040), previous antiplatelet therapy showed reduced mortality (HR 0.098, p = 0.039). CONCLUSION: Although risk factors such as previous stroke, PAD, diabetes, renal insufficiency, and anemia were predictors for death in all patients and patients < 75 years, in the elderly only arterial hypertension increased, whereas treatment with platelet inhibitors decreased mortality.

[Infective endocarditis : emergency treatment and long-term surveillance]. / Infektiöse Endokarditis : Notfallbehandlung und Langzeitbetreuung.

Infective endocarditis is a serious disease that is often diagnosed with a considerable delay in clinical practice and therefore has a high mortality rate; therefore, early diagnosis and antibiotic treatment are extremely important. Epidemiological shifts in the age profile, new risk factors and the increasing use of intravascular prosthetic materials have led to changes in the microbial spectrum and clinical symptoms, which must be taken into account in the diagnostic efforts and therapy. Nonspecific symptoms and the increase in nosocomial endocarditis, especially in critically ill and immunocompromised patients require a high level of diagnostic expertise. With diagnostic algorithms based on guideline recommendations antibiotic treatment has to be initiated as early as possible. For patients with severe infective endocarditis a cardiac surgeon has to be involved from an early stage of the disease as in about 50 % of cases conservative antibiotic therapy alone does not alleviate the infection. Also early surgical treatment should be sought with the onset of complications. After effective treatment and patient survival there will always be an increased risk of suffering from renewed endocarditis. This is taken into account in the new recommendations of the European Society of Cardiology for the prevention of infective endocarditis.

Pathophysiology, diagnosis, and treatment of infarction-related cardiogenic shock.

Cardiogenic shock is characterized by inadequate tissue perfusion due to cardiac dysfunction, and it is often caused by acute myocardial infarction. The mortality rate in patients with cardiogenic shock is still very high (i.e., 50-60%). The pathophysiology of cardiogenic shock involves a vicious spiral circle: ischemia causes myocardial dysfunction, which in turn aggravates myocardial ischemia. Myocardial stunning and/or hibernating myocardium can enhance myocardial dysfunction, thus, worsening the cardiogenic shock. Low perfusion pressures with global ischemia leads to multiorgan dysfunction. Ischemia and reperfusion can result in systemic inflammation or within the first few days sepsis due to the translocation of bacteria or bacterial toxins from the intestines, which can result in increased mortality. The key to an optimal treatment of cardiogenic shock patients is a structured approach: (1) rapid diagnosis and prompt initiation of therapy to increase blood pressure and augment cardiac output with subsequently improved perfusion. (2) Rapid coronary revascularization is of critical importance. Using this approach, mortality can be reduced. In many hospitals, initial stabilization is achieved by intraaortic balloon counterpulsation (IABP). However, evidence for improved survival from randomized studies on the use of IABP in combination with PCI is lacking. (3) In order to achieve adequate perfusion, dobutamine and sometimes in combination with norepinephrine might be necessary. Recent studies have shown that the calcium sensitizer levosimendan in cardiogenic shock can be a useful addition to medical therapy. In this overview, epidemiology, pathophysiology, and guideline-oriented treatment strategies for cardiogenic shock are presented.

[Cardiac biomarkers in perioperative medicine : significance for noncardiac surgery patients]. / Kardiale Biomarker in der perioperativen Medizin : Stellenwert bei nichtherzchirurgischen Patienten.

Perioperative detection of cardiac biomarkers may help to identify patients at risk. Whether detection of these markers will be recommended in the preoperative setting for patients with cardiac diseases in the future has to be discussed as large prospective trials on this topic are missing. For preoperative evaluation of cardiac insufficiency quantification of brain natriuretic peptide (BNP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are useful markers. Troponin is the marker of choice for detection of myocardial ischemia/infarction in the postoperative setting. In unstable patients coronary angiography and/or percutaneous coronary intervention (PCI) are indicated. However, in stable patients the decision for coronary angiography and/or PCI has to be made in each patient individually after interdisciplinary discussion between anesthesiologists, cardiologists and surgeons.

A lifetime of challenges: real-life decision outcomes in early- and late-onset suicide attempters.

BACKGROUND: People who have attempted suicide display suboptimal decision-making in the lab. Yet, it remains unclear whether these difficulties tie in with other detrimental outcomes in their lives besides suicidal behavior. We hypothesize that this is more likely the case for individuals who first attempted suicide earlier than later in life. METHODS: A cross-sectional case-control study of 310 adults aged ≥ 50 years (mean: 63.9), compared early- and late-onset attempters (first attempt < 55 vs. ≥ 55 years of age) to suicide ideators, non-suicidal depressed controls and non-psychiatric healthy controls. Participants reported potentially avoidable negative decision outcomes across their lifetime, using the Decision Outcome Inventory (DOI). We employed multi-level modeling to examine group differences overall, and in three factor-analytically derived domains labeled Acting Out, Lack of Future Planning, and Hassles. RESULTS: Psychopathology predicted worse decision outcomes overall, and in the more serious Acting Out and Lack of Future Planning domains, but not in Hassles. Early-onset attempters experienced more negative outcomes than other groups overall, in Lack of Future Planning, and particularly in Acting Out. Late-onset attempters were similar to depressed controls and experienced fewer Acting out outcomes than ideators. LIMITATIONS: The cross-sectional design precluded prospective prediction of attempts. The assessment of negative outcomes may have lacked precision due to recall bias. CONCLUSIONS: Whereas early-onset suicidal behavior is likely the manifestation of long-lasting decision-making deficits in several serious aspects of life, late-onset cases appear to function similarly to non-suicidal depressed adults, suggesting that their attempt originates from a more isolated crisis.

[Core curriculum Medical intensive care medicine of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN)]. / Curriculum Internistische Intensivmedizin.

Medical intensive care medicine treats patients with severe, potentially life-threatening diseases covering the complete spectrum of internal medicine. The qualification in medical intensive care medicine requires a broad spectrum of knowledge and skills in medical intensive care medicine, but also in the general field of internal medicine. Both sides of the coin must be taken into account, the treatment with life-sustaining strategies of the acute illness of the patient and also the treatment of patient's underlying chronic diseases. The indispensable foundation of medical intensive care medicine as described in this curriculum includes basic knowledge and skills (level of competence I-III) as well as of behavior and attitudes. This curriculum is primarily dedicated to the internist in advanced training in medical intensive care medicine. However, this curriculum also intends to reach trainers in intensive care medicine and also the German physician chambers with their examiners, showing them which knowledge, skills as well as behavior and attitudes should be taught to trainees according to the education criteria of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN).

Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression.

Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive. In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression. Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production. Furthermore, treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice, as assessed by both enhanced pause (PenH) responses and pulmonary resistance determined by body plethysmography. These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of airway hyperresponsiveness such as in asthma. This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine.

[Therapeutic strategies in acute decompensated heart failure and cardiogenic shock]. / Diagnostik und Therapie bei akut dekompensierter Herzinsuffizienz und kardiogenem Schock.

As the population of elderly people is increasing, the number of patients requiring hospitalization for acute exacerbations is rising. Traditionally, these episodes of hemodynamic instability were viewed as a transient event characterized by systolic dysfunction, low cardiac output, and fluid overload. Diuretics, along with vasodilator and inotropic therapy, eventually became elements of standard care. In a multicenter observational registry (ADHERE--Acute Decompensated Heart Failure National Registry) of more than 275 hospitals, patients with acute decompensated heart failure were analyzed for their characteristics and treatments options. These data have shown that this population consists of multiple types of heart failure, various forms of acute decompensation, combinations of comorbidities, and varying degrees of disease severity. The challenges in the treatment require multidisciplinary approaches since patients typically are elderly and have complex combinations of comorbidities. So far only a limited number of drugs is currently available to treat the different groups. Over the past years it was shown that even "standard drugs" might be deleterious by induction of myocardial injury, worsening of renal function or increasing mortality upon treatment. Therefore, based on pathophysiology, different types of acute decompensated heart failure require specialized treatment strategies.

[Imaging in intensive care units]. / Bildgebung auf der Intensivstation.

Imaging is essential in the diagnosis and treatment of critically ill patients. Although bedside ultrasound and chest x­rays are the major tools in the initial assessment, there are a variety of imaging options available to physicians in the intensive care unit such as computed tomography, magnetic resonance imaging, or nuclear medicine. Bedside diagnostic tools or radiology intervention procedures also play an important role in the management of critically ill patients. The choice of imaging modality is sometimes difficult and should be based on current recommendations or guidelines, available equipment, and the experience of the examiner. With the increasing importance of costs, the diagnostic and therapeutic benefits of the imaging process must be maximized in line with minimizing costs. The various indications, strengths, and weaknesses of the imaging modalities are summarized and the diagnostic findings using clinical examples are discussed. The focus of this article is on imaging of the thorax and the diagnostic imaging methods used in the intensive care unit.

[Presumed consent for organ donation? : A survey among members of the German Society of Medical Intensive Care and Emergency Medicine]. / Widerspruchslösung bei der Organspende? : Eine Umfrage bei Mitgliedern der Deutschen Gesellschaft für internistische Intensivmedizin und Notfallmedizin.

BACKGROUND: Since 2010, the number of organ donations has decreased by 30% in Germany; however, stricter organizational structures in clinics and improved payment for hospital services associated with organ removal should increase the current decline in the number of organ donations in Germany. In addition, the Federal Minister of Health proposed introduction of the double presumed consent solution for organ donation. This proposal is currently being discussed very controversially. Against this background, we conducted an online survey of all members of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN) in order to evaluate the attitude towards organ donation. METHOD: The present work is an anonymous online survey among the members of DGIIN, which took place from 10-23 September 2018. In addition to a few demographic queries, the personal opinion on the regulation of organ donation was collected. RESULTS: A total of 1019 (51.9%) of 1964 invited DGIIN members took part at the survey: 79.3% of the participants were male; average age 47.5 ± 11.2 years; 97.7% were physicians, of whom 89.2% were specialists and 62.7% had the additional degree in critical care; 20.6% voted for the current decision-making solution, 43.1% for the presumed consent, 33.1% for the double presumed consent, whereas 3.2% of the respondents were uncertain in their decision. CONCLUSION: A clear majority of the surveyed members of DGIIN support the concept of presumed consent.

Vasopressors for acute myocardial infarction complicated by cardiogenic shock.

Several international evidence-based guidelines reveal the lack of evidence on the treatment of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) for all recommended therapies. We included 6 studies with 842 eligible patients and one ongoing study. Three different adrenergic agents (norepinephrine, dopamine, epinephrine), vasopressin and the NOS inhibitor tilarginine were compared in 4 different combinations. On the small basis of all available evidence we can state that there is no evidence to use tilarginene, some evidence to avoid dopamine due to increased rates of arrhythmias, but some evidence, which suggests to prefer norepinephrine in comparison to epinephrine as vasopressor.

Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation.

BACKGROUND AND PURPOSE: The Na(+)/H(+) exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca(2+) overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. EXPERIMENTAL APPROACH: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 micro ml(-1)) superfusion or ischaemia (by haemorrhagic shock for 60 min) and reperfusion (90 min). KEY RESULTS: Treatment with cariporide (10 mg kg(-1) i.v.) significantly reduced leukocyte rolling, adhesion and extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte rolling (54+/-6.2 to 2.4+/-1.0 cells min(-1), P<0.01), adherence (6.3+/-1.9 to 1.2+/-0.4 cells 100 microm(-1), P<0.01) and extravasation (9.1+/-2.1 to 2.4+/-1.1 cells per 20 x 100 microm perivascular space, P<0.05), following haemorrhagic shock induced systemic ischaemia and reperfusion. The cell adhesion molecule P-selectin showed a profound decrease in endothelial expression following cariporide administration in both thrombin and I/R stimulated groups (35.4+/-3.2 vs 14.2+/-4.1% P-selectin positive cells per tissue section, P<0.01). CONCLUSIONS AND IMPLICATIONS: The NHE inhibitor cariporide is known to limit reperfusion injury by controlling Ca(2+) overload but these data are novel evidence for a vasculoprotective effect of NHE inhibition at all levels of leukocyte activation, an effect which is likely to be mediated at least in part by a reduction of P-selectin expression.

Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury.

BACKGROUND AND PURPOSE: Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage. EXPERIMENTAL APPROACH: We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10,000 Ukg(-1)) or its vehicle were injected 5 min prior to the start of reperfusion. KEY RESULTS: Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11+/-2.7% necrosis as percentage of area at risk after aprotinin; 24+/-3.1% after vehicle; P<0.05) and plasma creatine kinase activity (12.2+/-1.5 and 17.3+/-2.3 IU g(-1) protein in aprotinin and vehicle groups, respectively, P<0.05). PMN infiltration (assessed by myeloperoxidase activity) was significantly decreased in aprotinin-treated animals compared to vehicle (P<0.01). Histological analysis also revealed a substantial increase in PMN infiltration following MI+R and this was significantly reduced by aprotinin therapy (44+/-15 vs 102+/-2 PMN mm2 in aprotinin vs vehicle-treated animals, P<0.05). In parallel in vitro experiments, aprotinin inhibited neutrophil-endothelium interaction by reducing PMN adhesion on isolated, activated aortic endothelium. Finally, immunohistochemical analysis illustrated aprotinin significantly reduced myocardial apoptosis following MI+R. CONCLUSIONS AND IMPLICATIONS: Inhibition of serine proteases by aprotinin inhibits an inflammatory cascade initiated by MI+R. The cardioprotective effect appears to be at least partly due to reduced PMN adhesion and infiltration with subsequently reduced myocardial necrosis and apoptosis.

[Hemorrhage under direct oral anticoagulants : Occurrence and treatment in intensive care patients]. / Blutungen unter direkten oralen Antikoagulanzien : Auftreten und Therapie bei Intensivpatienten.

The use of anticoagulants is associated with an increased risk of bleeding and nevertheless bleeding complications can be lifethreatening. The focus is on bleeding under direct oral anticoagulants (DOAC) because antidotes and specific measures are lacking for some DOACs. Furthermore, routinely carried out clotting tests cannot be used to determine the degree of anticoagulation under DOACs. Therefore, it becomes difficult to determine whether the coagulation inhibition effect is present. This article presents the treatment of hemorrhage in patients with DOACs in the intensive care unit. Further, the indications for DOACS and details of administration and monitoring are presented.

[Palliative care : Challenges in the intensive care unit]. / Palliativbehandlung : Herausforderungen auf der Intensivstation.

Intensive care unit (ICU) stays often result due to an acute, potentially life-threatening illness or aggravation of a chronic life-threatening illness. In many cases, ICU patients die after life-sustaining treatments are withdrawn or withheld. When patients are asked, they prefer to die at home, although logistic and medical problems often prevent this. Therefore, attention focuses on care at the end of life in the ICU. Despite many efforts to improve the quality of care, evidence suggests that the quality in hospitals varies significantly and that palliative care in the ICU has not significantly improved over time. In this review, aspects of palliative care that are specific to ICU patients are discussed.