[Cardiovascular therapy for sepsis: when, how and how much?] / Kreislauftherapie bei Sepsis ­ wann, wie und wie viel?

The management of hemodynamic instability in the context of sepsis or septic shock is at the forefront in emergency care as well as in the intensive care unit. Cardiovascular instability has a dramatic impact on the rate of organ complications and mortality from sepsis. According to the guideline for the treatment of sepsis, mean arterial pressure should not fall below 65 mm Hg. Crystalloid balanced fluid and catecholamines are the cornerstones of therapy management for septic cardiovascular instability. In this article, the most important points of what, when and how much regarding circulation therapy are presented and critically discussed.

Pelvic cellulitis caused by Raoultella planticola in a neutropenic patient.

Raoultella planticola is a gram-negative, encapsulated, aerobic bacterium within the Enterobacteriaceae family. It has been primarily described as pathogen in cases with pneumonia and gastrointestinal infections. Here we describe a case of severe pelvic cellulitis in a patient with neutropenia following induction therapy for myeloid sarcoma. The patient experienced a septic shock and was treated successfully with antibiotic therapy. A literature review is provided to put this case in context with previous reports on R. planticola. This report highlights that awareness for uncommon pathogens is crucial in the clinical management of infections in neutropenic patients.

[Evolving Epidemiology of Home Mechanical Ventilation: A Rapidly Growing Challenge for Patient Care]. / Epidemiologische Entwicklung der außerklinischen Beatmung: Eine rasant zunehmende Herausforderung für die ambulante und stationäre Patientenversorgung.

BACKGROUND: Home mechanical ventilation is dramatically evolving in Germany. Patients with non-invasive and invasive ventilation are increasingly treated at home. In-hospital treatment of these patients is also necessary either for control visits or the management of acute medical problems. However, the development of in-hospital patient care, morbidity and mortality of these patients is unknown. METHODS: All patients with long-term dependence on mechanical ventilation for more than three months requiring hospitalisation between 2006 and 2016 were analysed (data obtained from the Federal Statistical Office of Germany). RESULTS: There was an exponential increase in the number of in-patients with long-term dependence of mechanical ventilation. While 24 845 patients were treated in-hospital in 2006, 86 117 patients were treated in 2016. Correspondingly, mortality decreased from 13.2 % (2006) to 5.7 % (2016). In addition, in 2016 47 % of all patients were treated on the intensive care or high dependency care unit. Overall, patients had been severely ill, as there were plenty of medical and neurological co-morbidities. The most common diagnosis was COPD with 58 % of all cases, followed by several cardiology diagnosis. A high number of patients had an impairment of renal function (24 %), in part requiring dialysis. CONCLUSIONS: The rapid development of home mechanical ventilation substantially impacts on the development of the hospital landscape in Germany. The exponential increase of these care-intensive patients is challenging for the health care system and requires a discussion about its limits.

Consensus statement for cancer patients requiring intensive care support.

This consensus statement is directed to intensivists, hematologists, and oncologists caring for critically ill cancer patients and focuses on the management of these patients.

[Cancer patients in operative intensive care medicine]. / Krebspatienten in der operativen Intensivmedizin.

Cancer is one of the leading causes of death worldwide. New targeted and individualized therapies and drugs provide a survival benefit for an increasing number of patients, but can also cause severe side effects. An increasing number of oncology patients are admitted to intensive care units (ICU) because of cancer-related complications or treatment-associated side effects. Postoperative care, respiratory distress and sepsis are the leading causes for admission. Tumor mass syndromes and tumor lysis may require urgent treatment. Traditional anticancer chemotherapy is associated with infections and immunosuppression. Newer agents are generally well-tolerated and side effects are mild or moderate, but overwhelming inflammation and autoimmunity can also occur. Cellular treatment, such as with chimeric antigen receptor modified T­cells, monoclonal and bispecific antibodies targeting immune effectors and tumor cells are associated with cytokine release syndrome (CRS) with hypotension, skin reactions and fever. It is related to excessively high levels of inflammatory cytokines. Immune checkpoint inhibitors can lead to immune-related adverse events (IRAEs), such as colitis and endocrine disorders. Noninfectious respiratory complications, such as pneumonitis can also occur. Recent studies revealed that short-term and medium-term survival of cancer patients is better than previously expected. In this review article we summarize diagnostic and treatment strategies for common life-threatening complications and emergencies requiring ICU admission. Furthermore, strategies for rational admission policies are presented.

[Diagnostic management of fever]. / Diagnostisches Management von Fieber.

Fever is a symptom of a wide range of diseases. Its diagnostic management is of crucial importance, whereby the interface between general practitioner and hospital plays an important role. The family practitioner is of particular importance in the detection of life-threatening or complex situations involving fever. The diagnostic algorithm presented here can serve as the basis for rapid and targeted diagnostics. Good communication between the doctor and the hospital doctor is mandatory.

Influenza virus infections in patients with malignancies -- characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO).

Influenza virus infections (IVI) may pose a vital threat to immunocompromised patients such as those suffering from malignancies, but specific data on epidemiology and outcome in these patients are scarce. In this study, we collected data on patients with active cancer or with a history of cancer, presenting with documented IVI in eight centres in Germany. Two hundred and three patients were identified, suffering from haematological malignancies or solid tumours; 109 (54 %) patients had active malignant disease. Influenza A was detected in 155 (77 %) and Influenza B in 46 (23 %) of patients (genera not determined in two patients). Clinical symptoms were consistent with upper respiratory tract infection in 55/203 (27 %), influenza-like illness in 82/203 (40 %), and pneumonia in 67/203 (33 %). Anti-viral treatment with oseltamivir was received by 116/195 (59 %). Superinfections occurred in 37/203 (18 %), and admission on an intensive care unit was required in 26/203 (13 %). Seventeen patients (9 %) died. Independent risk factors for death were delayed diagnosis of IVI and bacterial or fungal superinfection, but not underlying malignancy or ongoing immunosuppression. In conclusion, patients with IVI show high rates of pneumonia and mortality. Early and rapid diagnosis is essential. The high rate of pneumonia and superinfections should be taken into account when managing IVI in these patients.

Candidemia in the intensive care unit: analysis of direct treatment costs and clinical outcome in patients treated with echinocandins or fluconazole.

Direct treatment costs caused by candidemia in German intensive care unit (ICU) patients are currently unknown. We analyzed treatment costs and the impact of antifungal drug choice. Comprehensive data of patients who had at least one episode of candidemia while staying in the ICU between 01/2005 and 12/2010 were documented in a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). A detailed analysis of all disease-associated treatment costs was performed. Patients treated with echinocandins (i.e., anidulafungin, caspofungin, micafungin) or fluconazole were analyzed separately and compared. Forty-one and 64 patients received echinocandins and fluconazole, respectively. The mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 114 (95 % confidence interval [CI]: 106-122) vs. 95 (95 % CI: 90-101, p = <0.001). Twenty-three (56 %) and 33 (52 %, p = 0.448) patients survived hospitalization, while 17 (41 %) and 22 (34 %, p = 0.574) survived one year after diagnosis. In the echinocandin and fluconazole groups, the mean costs per patient of ICU treatment were 20,338 (95 % CI: 12,893-27,883) vs. 11,932 (95 % CI: 8,016-15,849, p = 0.110), and the total direct treatment costs per patient were 37,995 (95 % CI: 26,614-49,376) vs. 22,305 (95 % CI: 16,817-27,793, p = 0.012), resulting in daily costs per patient of 1,158 (95 % CI: 1,036-1,280) vs. 927 (95 % CI: 828-1,026, p = 0.001). Our health economic analysis shows the high treatment costs of patients with candidemia in the ICU. Sicker patients had a prolonged hospitalization and were more likely to receive echinocandins, leading to higher treatment costs. Outcomes were comparable to those achieved in less sick patients with fluconazole.

[Intensive care management of hematological and oncological patients]. / Intensivmedizinisches Management hämatologischer und onkologischer Patienten.

Management of critically ill cancer patients warrants stringent admission criteria and clear concepts concerning duration and limits of intensive care. Recent developments in mechanical ventilation and sepsis therapy can easily be used to improve the outcome of critically ill cancer patients. The incidence and overall prognosis of cancer is constantly growing and, thus, the number of critically ill cancer patients is increasing. Furthermore, novel oncology drugs-in particular immune modulators-produce unexpected and substantial side effects. Therefore, the development of an interdisciplinary algorithm by oncologists and intensivists remains an important and dynamic challenge.

[Neutropenia and sepsis]. / Neutropenie und Sepsis.

The clinical management of neutropenic infections represents a great diagnostic and therapeutic challenge. Established sepsis criteria only partially reflect the neutropenic setting. Diagnostic procedures are frequently impaired by thrombocytopenia and progressive respiratory insufficiency. Increased tendency to bleed, engraftment, and fulminant progression represent major therapeutic challenges. Thus, crucial for the diagnosis and therapy of neutropenic sepsis are clear and well-communicated algorithms, rapid action, and close collaboration between oncologists and intensivists.

[Proposal for participation in intensive care and emergency medicine studies for patients unable to give informed consent (Cologne Model)]. / Vorschlag für ein Verfahren zur Teilnahme an intensiv- und notfallmedizinischen Studien bei nichteinwilligungsfähigen Patient*innen (Kölner Modell).

When conducting clinical trials in intensive care and emergency medicine, physicians, ethics committees, and legal experts have differing views regarding the inclusion of patients who are incapable of giving consent. These different views on the participation of patients who are not capable of giving consent also complicate how clinical trials are prepared and conducted. Based on the results of a literature search, a consensus model (Cologne Model) was developed by physicians performing clinical research, ethics committees, and lawyers in order to provide patients, those scientifically responsible for the study, ethics committees, and probate (guardianship) judges with a maximum of patient safety and legal certainty, while simultaneously enabling scientific research.

[The critically ill CAR T-cell patient : Relevant toxicities, their management and challenges in critical care]. / Der kritisch kranke Patient nach CAR-T-Zell-Therapie : Relevante Nebenwirkungen, deren Management und Herausforderungen an die Intensivmedizin.

BACKGROUND: CAR­T cell therapy has been implemented as clinical routine treatment option during the last decade. Despite beneficial outcomes in many patients severe side effects and toxicities are seen regularly that can compromise the treatment success. METHODS: Literature review: CAR T­cell therapy, toxicities and their management RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) are seen regularly after CAR T­cell treatment. CRS symptoms can range from mild flu-like symptoms to severe organ dysfunction requiring vasopressor therapy, mechanical ventilation and other intensive care support. ICANS symptoms usually develop later and can range from disorientation and aphasia to potentially life-threatening brain edema. IL­6 is a key factor in the pathophysiology of CRS. The pathophysiology of ICANS is not fully understood. The ASTCT consensus grading is recommended to stratify patients for different management options. An interdisciplinary team including hematologist, intensivist, neurologists and other specialties is needed to optimize the treatment. DISCUSSION: Severe and potentially life-threatening toxicities occur regularly after CAR T­cell therapy. Treatment strategies for CRS and ICANS still need to be evaluated prospectively. Due to the increasing number of patients treated with CAR T­cells the number of patients requiring temporary intensive care management due to CRS and ICANS is expected to increase during the next years.

[Prioritization of intensive medical treatment places - Concept proposal]. / Priorisierung intensivmedizinischer Behandlungsplätze ­ Konzeptvorschlag.

In the situation of a shortage of ventilation beds, ethically justifiable, transparent and comprehensible decisions must be made. This concept proposes that all patients are first intubated depending on necessity and then assessed by a triage team afterwards. In this situation newly admitted COVID patients compete with newly admitted Non-COVID patients as well as patients already treated in intensive care units for a ventilator. The combination of short-term and long-term prognoses should enable the interprofessional triage team to make comprehensible decisions. The aim of the prioritization concept is to save as many human lives as possible and to relieve the treatment team of the difficult decision on prioritization.

[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).

Multiple malignant diseases in a patient with Rothmund-Thomson syndrome with RECQL4 mutations: Case report and literature review.

RECQL4 mutations cause genetic instability and increase the risk of malignant disease. We report on a patient with compound heterozygosity for two novel RECQL4 mutations: mutation c.1919_1924delTCACAG, p.L640_A642delinsP in exon 12 of the RECQL4 gene and mutation c.1704+1G>A in intron 10 of the RECQL4 gene. He subsequently developed large cell anaplastic T cell lymphoma at the age of 9 years, diffuse large cell B lymphoma and osteosarcoma when he was 14 years old, and finally acute lymphatic leukemia when he was 21 years old. The most remarkable clinical features are young age, spontaneous remission of diffuse large cell lymphoma, and severe CNS and skin toxicity of cytotoxic treatment.

[CARs, CRS and neurotoxicity: severe complications after administration of immunotherapy : Essentials for intensivists]. / CAR, CRS und Neurotoxizität: schwere Komplikationen der Immuntherapie : Was der Intensivmediziner wissen muss.

BACKGROUND: The development of chimeric antigen receptor (CAR) T­cells has shown promising results in relapsed/refractory B­cell acute lymphoblastic leukemia/lymphoma (B-ALL) and diffuse large cell B­cell lymphoma. Complications, especially cytokine release syndrome (CRS) and CAR T­cell related encephalopathy syndrome (CRES), can be life threatening. The management of both plays a key role in CAR T­cell therapy. OBJECTIVES: Diagnosis, clinical presentation and development of complications in the treatment with CAR T­cells. MATERIALS AND METHODS: Summary of incidence, mortality and treatment of severe complications after administration of CAR T­cells referring to current studies and therapy recommendations. RESULTS: Complications after administration of CAR T­cells, especially CRS and CRES, can be life threatening. The timely identification of side effects and their appropriate treatment usually leads to complete recovery. CONCLUSIONS: Using a therapy algorithm in the treatment with CAR T­cells allows safe management of toxicities and can be helpful in recognizing them in time.