Critical care : the official journal of the Critical Care Forum
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Randomized Controlled Trial
Persistent organ dysfunction plus death: a novel, composite outcome measure for critical care trials.
Due to resource limitations, few critical care interventions have been rigorously evaluated with adequately powered randomized clinical trials (RCTs). There is a need to improve the efficiency of RCTs in critical care so that more definitive high quality RCTs can be completed with the available resources. The objective of this study was to validate and demonstrate the utility of a novel composite outcome measure, persistent organ dysfunction (POD) plus death, for clinical trials of critically ill patients. ⋯ POD + death may be a valid composite outcome measure and compared to mortality endpoints, may reduce the sample size requirements of clinical trials of critically ill patients. Further validation in larger clinical trials is required.
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Multicenter Study
Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study.
Neutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials. ⋯ The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.
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Randomized Controlled Trial
Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury.
Preclinical studies have shown that the endogenous nucleoside adenosine prevents excessive tissue injury during systemic inflammation. We aimed to study whether endogenous adenosine also limits tissue injury in a human in vivo model of systemic inflammation. In addition, we studied whether subjects with the common 34C > T nonsense variant (rs17602729) of adenosine monophosphate deaminase (AMPD1), which predicts increased adenosine formation, have less inflammation-induced injury. ⋯ Human experimental endotoxemia induces an increase in circulating cytokine levels and subclinical endothelial and renal injury. Although the plasma adenosine concentration is elevated during systemic inflammation, co-administration of caffeine or the presence of the 34C > T variant of AMPD1 does not affect the observed subclinical organ damage, suggesting that adenosine does not affect the inflammatory response and subclinical endothelial and renal injury during human experimental endotoxemia.
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Infections remain among the most important concerns in critically ill patients. Early and reliable diagnosis of infection still poses difficulties in this setting but also represents a crucial step toward appropriate antimicrobial therapy. ⋯ Rapid infection diagnosis, antibiotic dosing and optimization through pharmacologic indices, progress in the implementation of effective antimicrobial stewardship and infection control programs, and management of fungal infections are some of the most relevant issues in this special patient population. During the last 18 months, Critical Care and other journals have provided a wide array of descriptive and interventional clinical studies and scientific reports helping clinical investigators and critical care physicians to improve diagnosis, management, and therapy of infections in critically ill patients.
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The concept of frailty has been defined as a multidimensional syndrome characterized by the loss of physical and cognitive reserve that predisposes to the accumulation of deficits and increased vulnerability to adverse events. Frailty is strongly correlated with age, and overlaps with and extends aspects of a patient's disability status (that is, functional limitation) and/or burden of comorbid disease. The frail phenotype has more specifically been characterized by adverse changes to a patient's mobility, muscle mass, nutritional status, strength and endurance. ⋯ Owing to the theoretical similarities in frailty between geriatric and critically ill patients, this concept may have clinical relevance and may be predictive of outcomes, along with showing important interaction with several factors including illness severity, comorbid disease, and the social and structural environment. We believe studies of frailty in critically ill patients are needed to evaluate how it correlates with outcomes such as survival and quality of life, and how it relates to resource utilization, such as length of mechanical ventilation, ICU stay and duration of hospitalization. We hypothesize that the objective measurement of frailty may provide additional support and reinforcement to clinicians confronted with end-of-life decisions on the appropriateness of ICU support and/or withholding of life-sustaining therapies.