Organ Support Therapy Research Articles

Activated protein C and hospital mortality in septic shock: A propensity-matched analysis*

Evidence regarding the efficacy and safety of human recombinant activated protein C in severe sepsis is limited, especially outside of clinical trials. We sought to compare the outcomes of patients with septic shock who received early treatment with activated protein C to those who did not. A retrospective cohort study at 404 U.S. hospitals. We studied 33,749 patients with sepsis who were admitted to intensive care and administered antibiotics and vasopressors within 2 days of admission. Hospital mortality, intracranial and gastrointestinal hemorrhage, major transfusion. Compared to the entire cohort, the 1576 activated protein C-treated patients included in the matched analysis were younger (mean age, 61 vs. 67), more likely to be white (70% vs. 63%), and had fewer comorbidities. Treated patients were more likely to require mechanical ventilation (77% vs. 48%), to be administered two or more vasopressors (68% vs. 41%), to undergo pulmonary artery catheterization (9% vs. 4%), and to die in the hospital (40.7% vs. 38.1%). In a propensity-matched sample in which all covariates achieved balance, receipt of activated protein C was associated with reduced hospital mortality (40.7% vs. 46.6%; risk ratio, 0.87; 95% confidence interval, 0.80-0.95). This result was insensitive to a hypothetical unmeasured confounder. A similar pattern was observed across groups stratified by age and number of organ-supportive therapies. Four activated protein C-treated patients (0.25%) had hemorrhagic stroke, 107 (6.8%) had gastrointestinal bleeding, and five (0.3%) required major transfusion. Among patients presenting with septic shock, early treatment with activated protein C may be associated with reduced hospital mortality.

Prediction of acute volume loss in spontaneously breathing subjects

Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission.This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders.We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82–17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77–2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63–2.66) were not.In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.

Sepsis: Time has come to focus on the later stages

Despite numerous advances in intensive care medicine, sepsis remains a deadly disease. Today, conventional therapeutic approaches and mainstream scientific research mostly focus on symptomatic early goal directed organ support therapy. This includes fluid resuscitation, choice and timing of antibiotics and vasopressors, mechanical ventilation, and renal replacement strategies. Furthermore, great effort has been undertaken to investigate whether tightly controlled blood glucose levels, the application of corticosteroids, and early medication using activated protein C improves survival. However, most of these mainstream approaches have recently been shown unsuccessful in large-scale clinical trials. Current data now suggest that besides giving fluids, antibiotics, and symptomatic organ support, little - if at all - can be done to improve mortality from sepsis. This might be due to the fact that in the presence of modern intensive care medicine, most patients with severe sepsis or septic shock will survive the early "shock phase" of the disease. Mounting evidence suggests that in the course of the disease, most septic patients are then subjected to a secondary phase, which is characterised by a failure of cell-mediated immunity. This leads to repeated and uncontrolled infections, "chronic" multiple organ failure, and death in a large number of cases. Here we hypotheses that in order to profoundly influence survival from sepsis, future therapeutic efforts in the field should concentrate on this later "hypo-immune" stage of sepsis, associated immune phenomena, and novel immunomodulatory strategies. This may lead to the development of advanced immunomodulatory therapies available for widespread clinical use. Today, in the era of antibiotics and advanced organ system support therapy, it is not the bug that kills you- survival has become a matter of whether your cellular immune system can cope.

The future of extracorporeal support

Extracorporeal therapy has expanded significantly over the past few decades from solely artificial renal replacement therapy. In patients with multiple organ dysfunction syndrome, it becomes necessary to provide multiple organ support therapy. Technological advances have opened the door to a multifaceted intervention directed at supporting the function of multiple organs through the treatment of blood. Indications for "old" therapies such as hemofiltration and adsorption have been expanded, and using these therapies in combination further enhances blood detoxification capabilities. Furthermore, new devices are constantly in development. Nanotechnology allows us to refine membrane characteristics and design innovative monitoring/biofeedback devices. Miniaturization is leading down the path of wearable/implantable devices. With the incorporation of viable cells within medical devices, these instruments become capable not only of detoxification but synthetic functions as well, bringing us closer to the holy grail of complete replacement of organ function. This article provides a brief overview of current and future direction in extracorporeal support in the critical care setting.

Multiple organ support therapy for the critically ill patient in intensive care

Multiple organ dysfunction syndrome is the leading cause of mortality in critically ill patients and is responsible for a large amount of healthcare expenditure. Since the probability of death is directly correlated to the number of failing organs beyond the kidney and the degree of physiological derangement, a clinically sensible approach is to broaden the spectrum of physiological endpoints targeted by extracorporeal therapy. Blood is the vital element that regulates all body systems from cellular to organ level. Continuous renal replacement therapy (CRRT) has direct access to blood and thus to all organ systems. The evolution of CRRT from simple renal replacement to a multiorgan support therapy (MOST) is logical and should be the goal of extracorporeal blood purification in the intensive care unit. This review explains why MOST represents the most logical future conceptual and practical evolution of CRRT and illustrates the biological rationale, supplying animal and clinical evidence that confirms the ...

Acute renal failure and multiple organ dysfunction in the ICU: from renal replacement therapy (RRT) to multiple organ support therapy (MOST).

Renal replacement therapy (RRT) has evolved from the concept that we need to treat the dysfunction of a single organ (the kidney). As intensive care units have become more and more complex, it has become clear that the majority of patients with acute renal failure often have dysfunction of several other organs. In order to facilitate single organ support in this setting, continuous renal replacement therapy (CRRT) techniques have been developed. However, CRRT has opened the door to the concept that targeting renal support as the only goal of extracorporeal blood purification may be a simplistic view of our therapeutic aims. In this article we argue that it is now time to move from the simple goal of achieving adequate renal support. The proper goal of extracorporeal blood purification in ICU should be multi-organ support therapy (MOST). We explain why MOST represents the most logical future conceptual and practical evolution of CRRT and illustrates the biological rationale, supplying animal and clinical evidence that confirms the need to move rapidly in this direction theoretically, practically and technologically.