Category Archives: Review

Anticoagulant Therapy in Sepsis. The Importance of Timing

DOI: 10.1515/jccm-2017-0011

Sepsis associated coagulopathy is due to the inflammation-induced activation of coagulation pathways concomitant with dysfunction of anticoagulant and fibrinolytic systems, leading to different degrees of haemostasis dysregulation. This response is initially beneficial, contributing to antimicrobial defence, but when control is lost coagulation activation leads to widespread microvascular thrombosis and subsequent organ failure. Large clinical trials of sepsis-related anticoagulant therapies failed to show survival benefits, but posthoc analysis of databases and several smaller studies showed beneficial effects of anticoagulants in subgroups of patients with early sepsis-induced disseminated intravascular coagulation. A reasonable explanation could be the difference in timing of anticoagulant therapy and patient heterogeneity associated with large trials. Proper selection of patients and adequate timing are required for treatment to be successful. The time when coagulation activation changes from advantageous to detrimental represents the right moment for the administration of coagulation-targeted therapy. In this way, the defence function of the haemostatic system is preserved, and the harmful effects of overwhelming coagulation activation are avoided.

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The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

DOI: 10.1515/jccm-2017-0001

Sepsis is an injurious systemic host response to infection, which can often lead to septic shock and death. Recently, the immune-pathogenesis and genomics of sepsis have become a research topic focusing on the establishment of diagnostic and prognostic biomarkers. As yet, none have been identified as having the necessary specificity to be used independently of other factors in this respect. However the accumulation of current evidence regarding genetic variations, especially the single nucleotide polymorphisms (SNPs) of cytokines and other innate immunity determinants, partially explains the susceptibility and individual differences of patients with regard to the evolution of sepsis. This article outlines the role of genetic variation of some serum proteins which have the potential to be used as biomarker values in evaluating sepsis susceptibility and the progression of the condition.

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Extracorporeal Life Support and New Therapeutic Strategies for Cardiac Arrest Caused by Acute Myocardial Infarction – a Critical Approach for a Critical Condition

DOI: 10.1515/jccm-2016-0025

This review summarizes the most recent developments in providing advanced supportive measures for cardiopulmonary resuscitation, and the results obtained using these new therapies in patients with cardiac arrest caused by acute myocardial infarction (AMI). Also detailed are new approaches such as extracorporeal cardiopulmonary resuscitation (ECPR), intra-arrest percutaneous coronary intervention, or the regional models for systems of care aiming to reduce the critical times from cardiac arrest to initiation of ECPR and coronary revascularization.

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Sepsis-Associated Coagulopathy

DOI: 10.1515/jccm-2016-0024

Systemic inflammatory activation in sepsis often leads to coagulation activation, but the relationship is bilateral, as coagulation also modulates the inflammatory response. This close associate has significant consequences for the pathogenesis of microvascular thrombosis and organ dysfunction in sepsis. While coagulation activation can be beneficial for immune defense, it can also be detrimental once it becomes widespread and uncontrolled. The knowledge of the pathophysiologic mechanisms involved in the interaction between infection and coagulation may lead to the better timing for the administration of targeted antithrombotic therapies in septic patients. This brief review highlights the pathophysiologic pathways leading to the prothrombotic state in sepsis and the mechanisms that play a role in the interaction between infection and coagulation.

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The Diagnosis and Hemodynamic Monitoring of Circulatory Shock: Current and Future Trends

DOI: 10.1515/jccm-2016-0018

Circulatory shock is a complex clinical syndrome encompassing a group of conditions that can arise from different etiologies and presented by several different hemodynamic patterns. If not corrected, cell dysfunction, irreversible multiple organ insufficiency, and death may occur.  The four basic types of shock, hypovolemic, cardiogenic, obstructive and distributive, have features similar to that of hemodynamic shock.  It is therefore essential, when monitoring hemodynamic shock, to making accurate clinical assessments which will guide and dictate appropriate management therapy.
The European Society of Intensive Care has recently made recommendations for monitoring hemodynamic shock. The present paper discusses the issues raised in the new statements, including individualization of blood pressure targets, prediction of fluid responsiveness, and the use of echocardiography as the first means during the initial evaluation of circulatory shock.  Also, the place of more invasive hemodynamic monitoring techniques and future trends in hemodynamic and metabolic monitoring in circulatory shock, will be debated.

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Anemia in Intensive Care: A review of Current Concepts

DOI: 10.1515/jccm-2016-0017

Anemia in patients admitted to an intensive care unit is common and affects almost all critically ill patients. The intensivist is faced with the challenge of treating multifactorial etiologies, mainly bleeding and blood loss due to phlebotomy and decreased erythropoiesis. Red cell transfusion, the most common treatment for anemia, comes with associated risks, which may further reduce the chance of survival of these patients. The best evidence suggests the practice of restrictive RBC transfusion (transfusion at Hb<7 g/dl).
In this article, the etiopathogenesis of the anemia in critically ill is reviewed, and current opinion on the pros and cons of various management strategies are discussed with emphasize on restrictive transfusion policy.

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Much Ado About the New Definitions of Sepsis

DOI: 10.1515/jccm-2016-0015

Following the publication of the new definition of sepsis (Sepsis-3), a plethora of articles have been published in medical journals. Recognizing the epidemiological importance of the previous definitions, first issued in 1992 (Sepsis-1), and subsequently revised in 2001 (Sepsis-2), the most recent opinion emphasizes the failure “to provide adequate groups of patients with homogenous aetiologies, presentations and outcomes”, and blamed one of the causes “for the failure of several randomized controlled trials (RCTs), that tested the efficacy of adjuvant sepsis therapies”. This review summarizes the recent advances in sepsis definition.

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Cardiac Arrhythmias in a Septic ICU Population: A Review

DOI: 10.1515/jccm-2015-0027

Progressive cardiovascular deterioration plays a central role in the pathogenesis of multiple organ failure (MOF) caused by sepsis. Evidence of various cardiac arrhythmias in septic patients has been reported in many published studies. In the critically ill septic patients, compared to non-septic patients, new onset atrial fibrillation episodes are associated with high mortality rates and poor outcomes, amongst others being new episodes of stroke, heart failure and long vasopressor usage. The potential mechanisms of the development of new cardiac arrhythmias in sepsis are complex and poorly understood. Cardiac arrhythmias in critically ill septic patients are most likely to be an indicator of the severity of pre-existing critical illness.

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Invasive Candida Infections in the ICU: Diagnosis and Therapy

DOI: 10.1515/jccm-2015-0025

Invasive fungal infections have become a serious problem in the critically ill. One of the main reasons is the development of an immunocompromised condition. The most frequently found pathogens are Candida species. In order to provide adequate treatment, understanding this potentially life-threatening infection is mandatory. The aim of this summary is to view Candida infections from a different perspective and to give an overview on epidemiology, the range of pathophysiology from colonization to the invasive infections, and its impact on mortality. New therapeutic options will also be discussed and how these relate to current guidelines. Finally, the key issue of the choice of antifungal agents will be evaluated.

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Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

DOI: 10.1515/jccm-2015-0021

It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or non-responders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

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