Concept: Multiple organ dysfunction syndrome
Sepsis, severe sepsis, and septic shock represent increasingly severe systemic inflammatory responses to infection. Sepsis is common in the aging population, and it disproportionately affects patients with cancer and underlying immunosuppression. In its most severe form, sepsis causes multiple organ dysfunction that can produce a state of chronic critical illness characterized by severe immune dysfunction and catabolism. Much has been learnt about the pathogenesis of sepsis at the molecular, cell, and intact organ level. Despite uncertainties in hemodynamic management and several treatments that have failed in clinical trials, investigational therapies increasingly target sepsis induced organ and immune dysfunction. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, the rapid delivery of effective antibiotics, and other improvements in supportive care for critically ill patients. These improvements include lung protective ventilation, more judicious use of blood products, and strategies to reduce nosocomial infections.
Sepsis is a common cause of death in the intensive care unit with mortality up to 70% when accompanied by multiple organ dysfunction. Rapid diagnosis and the institution of appropriate antibiotic therapy and pressor support are therefore critical for survival. MicroRNAs are small non-coding RNAs that play an important role in the regulation of numerous cellular processes, including inflammation and immunity.
[This corrects the article on p. e42751 in vol. 7.].
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system.
Systemic inflammatory response syndrome (SIRS) and sepsis are now frequently identified by observations of vital signs and detection of organ failure during triage in the emergency room. However, there is less focus on the effect on patient outcome with better observation and treatment at the ward level.
Background The consensus definition of severe sepsis requires suspected or proven infection, organ failure, and signs that meet two or more criteria for the systemic inflammatory response syndrome (SIRS). We aimed to test the sensitivity, face validity, and construct validity of this approach. Methods We studied data from patients from 172 intensive care units in Australia and New Zealand from 2000 through 2013. We identified patients with infection and organ failure and categorized them according to whether they had signs meeting two or more SIRS criteria (SIRS-positive severe sepsis) or less than two SIRS criteria (SIRS-negative severe sepsis). We compared their characteristics and outcomes and assessed them for the presence of a step increase in the risk of death at a threshold of two SIRS criteria. Results Of 1,171,797 patients, a total of 109,663 had infection and organ failure. Among these, 96,385 patients (87.9%) had SIRS-positive severe sepsis and 13,278 (12.1%) had SIRS-negative severe sepsis. Over a period of 14 years, these groups had similar characteristics and changes in mortality (SIRS-positive group: from 36.1% [829 of 2296 patients] to 18.3% [2037 of 11,119], P<0.001; SIRS-negative group: from 27.7% [100 of 361] to 9.3% [122 of 1315], P<0.001). Moreover, this pattern remained similar after adjustment for baseline characteristics (odds ratio in the SIRS-positive group, 0.96; 95% confidence interval [CI], 0.96 to 0.97; odds ratio in the SIRS-negative group, 0.96; 95% CI, 0.94 to 0.98; P=0.12 for between-group difference). In the adjusted analysis, mortality increased linearly with each additional SIRS criterion (odds ratio for each additional criterion, 1.13; 95% CI, 1.11 to 1.15; P<0.001) without any transitional increase in risk at a threshold of two SIRS criteria. Conclusions The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death. (Funded by the Australian and New Zealand Intensive Care Research Centre.).
BACKGROUND:: In 1992, the first consensus definition of severe sepsis was published. Subsequent epidemiologic estimates were collected using administrative data, but ongoing discrepancies in the definition of severe sepsis produced large differences in estimates. OBJECTIVES:: We seek to describe the variations in prevalence and mortality of severe sepsis in the United States using four methods of database abstraction. We hypothesized that different methodologies of capturing cases of severe sepsis would result in disparate estimates of prevalence and mortality. DESIGN, SETTING, PARTICIPANTS:: Using a nationally representative sample, four previously published methods (Angus et al, Martin et al, Dombrovskiy et al, and Wang et al) were used to gather cases of severe sepsis over a 6-yr period (2004-2009). In addition, the use of new ICD-9 sepsis codes was compared with previous methods. MEASUREMENTS:: Annual national prevalence and in-hospital mortality of severe sepsis. RESULTS:: The average annual prevalence varied by as much as 3.5-fold depending on method used and ranged from 894,013 (300/100,000 population) to 3,110,630 (1,031/100,000) using the methods of Dombrovskiy et al and Wang et al, respectively. Average annual increase in the prevalence of severe sepsis was similar (13.0% to 13.3%) across all methods. In-hospital mortality ranged from 14.7% to 29.9% using abstraction methods of Wang et al and Dombrovskiy et al. Using all methods, there was a decrease in in-hospital mortality across the 6-yr period (35.2% to 25.6% [Dombrovskiy et al] and 17.8% to 12.1% [Wang et al]). Use of ICD-9 sepsis codes more than doubled over the 6-year period (158,722 - 489,632 [995.92 severe sepsis], 131,719 - 303,615 [785.52 septic shock]). CONCLUSION:: There is substantial variability in prevalence and mortality of severe sepsis depending on the method of database abstraction used. A uniform, consistent method is needed for use in national registries to facilitate accurate assessment of clinical interventions and outcome comparisons between hospitals and regions.
In order to investigate the hypothesis that bacterial translocation from the intestine contributes to death after multiple organ dysfunction syndrome (MODS), a sterile MODS model was studied.
After numerous negative randomized trials testing drugs for severe sepsis and/or septic shock, the blood purification approach remains one possibility. Many techniques have been proposed, having in common the goal to eliminate blood and/or plasma factors, supposed to play a negative role in outcomes. Among these, high dose of hemofiltration, high volume hemofiltration, high permeability hemofiltration and specific or non-specific hemoperfusion or hemoadsorption have been proposed. Until now, a poor level of proof has been published, questioning the pertinence of such a strategy. To have a chance to succeed, immune monitoring has to be performed to select suitable patients regarding their immune status, the intensity of inflammation and their cellular function. Because of the potential interaction with mediators and cell capture, Rimmelé and colleagues published the results obtained with an in vitro set up, testing different adsorption cartridges in comparison to hemofiltration. They nicely confirmed the complex impact on mediator levels and cell capture and phenotype. This is certainly a more systematic approach to better understand the action of such adsorbing cartridges, which has to be developed.
To evaluate the effects of pulse high-volume hemofiltration (PHVHF) on severe acute pancreatitis (SAP) with multiple organ dysfunction syndrome (MODS). Thirty patients were divided into two groups: PHVHF group and continuous venovenous hemofiltration (CVVH) group. They were evaluated in terms of clinical symptoms, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, simplified acute physiology (SAPS) II score and biochemical changes. The levels of IL-6, IL-10 and TNF-α in plasma were assessed by ELISA before and after treatment. The doses of dopamine used in shock patients were also analyzed. In the two groups, symptoms were markedly improved after treatment. Body temperature (BT), breath rate (BR), heart rate (HR), APACHE II score, SOFA score, SAPS II score, serum amylase, white blood cell count and C-reactive protein were decreased after hemofiltration (P < 0.05). The PHVHF group was superior to the CVVH group, especially in APACHE II score, CRP (P < 0.01), HR, temperature, SOFA score and SAPS II score (P < 0.05). The doses of dopamine for shock patients were also decreased in the two groups (P < 0.05), with more reduction in the PHVHF group than the CVVH group (P < 0.05). The levels of IL-6, IL-10 and TNF-α decreased (P < 0.05) in the PHVHF group more significantly than the CVVH group (P < 0.01). PHVHF appears to be superior to CVVH in the treatment of SAP with MODS.