Plasma interleukin-6 response is predictive for severity and mortality in canine systemic inflammatory response syndrome and sepsis

BACKGROUND: Sepsis is still a major cause of death in both human and veterinary medicine. Early diagnosis is essential for appropriate treatment. Identification of patients at risk for developing sepsis is already possible in human medicine through the measurement of plasma interleukin-6 (IL-6) levels. In veterinary medicine, however, this has been investigated only in canine experimental models. OBJECTIVES: The purpose of this study was to measure IL-6 plasma levels in dogs with naturally occurring systemic inflammatory response syndrome (SIRS) and sepsis and to analyze the value of IL-6 as a predictive parameter for severity and mortality. METHODS: Included in the study were 79 dogs that had been admitted to the small animal clinics of Munich and Berlin from July 2004 to July 2005 and that satisfied the diagnostic criteria for SIRS and sepsis as defined using established parameters. Measurement of plasma IL-6 levels on days 0, 1, and 2 was performed by the use of a colorimetric bioassay based on IL-6-dependent cell growth. RESULTS: Septic foci were identified in 43 patients (septic group), and 36 patients were enrolled in the SIRS group. The frequency of positive blood cultures was 11%. The overall mortality rate was 48%. Higher plasma IL-6 levels on the day of admission were significantly correlated with a more severe degree of disease, increased mortality rate, and earlier fatality. CONCLUSIONS: Plasma IL-6 concentration is predictive of outcome in canine SIRS and sepsis and may be a valuable laboratory parameter for assessing critically ill dogs.     

High‐mobility group box 1 as a surrogate prognostic marker in dogs with systemic inflammatory response syndrome

Objective – To evaluate various surrogate markers associated with the inflammatory and counter‐inflammatory responses with respect to mortality in dogs with systemic inflammatory response syndrome (SIRS). Design – Prospective observational study. Setting – Veterinary Teaching Hospital. Animals – Twenty‐eight dogs with naturally occurring diseases and SIRS from January 2007 to May 2009. Interventions – Upon admission to the veterinary hospital, history and baseline data from the physical examination, including parameters previously defined for meeting SIRS criteria, were documented. Heparinized blood samples were collected and plasma cytokines interleukin‐6 (IL‐6), IL‐10, and high‐mobility group box 1 (HMGB1) were measured by sandwich ELISA. Measurements and Main Results – In nonsurvivors, median plasma HMGB1 concentrations (0.718 μg/L, interquartile range [IQR]; 0.300–1.626 μg/L) and the ratio of HMGB1 to IL‐10 (2.236, IQR; 0.972–5.367) were significantly increased as compared with those found in survivors (0.300 μg/L, IQR; 0.300–0.312 μg/L for HMGB1; 1.017, IQR; 0.862–1.126 for the ratio of HMGB1 to IL‐10, P=0.007 and 0.024, respectively). Plasma IL‐6, IL‐10, and the ratio of IL‐6 to IL‐10 were not significantly different between groups. Among the parameters studied, HMGB1 and the ratio of HMGB1 to IL‐10 performed the best in discriminating outcome in dogs with SIRS according to receiver operator characteristic curve analysis. Conclusions – Increases in plasma HMGB1 concentration and the ratio of HMGB1 to IL‐10 may predict poorer outcomes in dogs with SIRS. The approach described may lead to reliable prognostic biomarkers and new therapeutic concepts in the study of SIRS in dogs.     

Use of C-reactive protein to predict outcome in dogs with systemic inflammatory response syndrome or sepsis

Background – There is a high mortality rate in patients with systemic inflammatory response syndrome (SIRS) or sepsis. Therefore, an early diagnosis and prognostic assessment is important for optimal therapeutic intervention. The objective of the study was to evaluate if baseline values and changes in serum C-reactive protein (CRP) might predict survival in dogs with SIRS and sepsis.
Design – Prospective study; July 2004 to July 2005.
Setting – Small Animal Clinic, Berlin, Clinic of Small Animal Medicine, Munich.
Animals – Sixty-one dogs.
Measurements and Main Results – For the CRP analysis blood was drawn on day 0, 1, and 2; CRP was measured using a commercial ELISA test kit. Thirteen dogs suffered from nonseptic SIRS and 48 dogs from sepsis. The 14-day survival rate was 61% (69% nonseptic SIRS, 58% sepsis). Serum CRP was higher in sick dogs compared with controls ( P <0.001). Over the 3-day period surviving dogs ( n =31) displayed a significantly greater decrease in CRP than nonsurvivors ( n =10) ( P =0.001). No correlation was found between the initial CRP concentrations and the survival rate. The changes in CRP corresponded to the survival rate ( P =0.01).
Conclusion – There was no significant relationship between the survival rate in dogs with nonseptic SIRS or sepsis and the initial serum CRP concentrations. There was a correlation between decreasing CRP concentrations and recovery from disease. However, the changes in CRP concentrations over a 3-day period correctly predicted survival in 94% of dogs and death in 30% of the dogs (false positive rate 22%).     

Plasma nitrate/nitrite concentrations in dogs with naturally developing sepsis and non-infectious forms of the systemic inflammatory response syndrome

The aim of this prospective observational study was to evaluate the differences in plasma nitrate/nitrite concentrations between dogs with sepsis and those with non-infectious forms of the systemic inflammatory response syndrome (SIRS). Eighteen dogs with sepsis, 20 dogs with SIRS and 29 healthy control dogs were enrolled. Blood samples were obtained from the dogs within 12 hours of admission to the University of Missouri Veterinary Medical Teaching Hospital (MU VMTH) Intensive Care Unit (ICU) in lithium heparin blood tubes. Plasma nitrate/nitrite concentrations were measured using the Greiss reaction. Plasma nitrate/nitrite concentrations at presentation, clinical parameters, organ dysfunction and in-hospital mortality were compared between groups. Plasma total nitrate/nitrite was significantly greater in the sepsis group compared with the control group (P=0.005) and SIRS group (P=0.037). There was no statistical difference in plasma nitrate/nitrite concentration between the SIRS and control groups (P=0.489). The sensitivity was 66.7 per cent (95 per cent CI, 41 to 87 per cent) and the specificity was 75.5 per cent (95 per cent CI, 61 to 87 per cent) for differentiating dogs with sepsis from dogs without sepsis.     

Multiple organ dysfunction syndrome in humans and dogs

Objective: To describe the clinical appearance and theories on the pathogenesis of multiple organ dysfunction syndrome (MODS) in humans, and to review the evidence suggesting that a similar syndrome occurs in critically ill dogs. Human‐based studies: Currently, there are a multitude of publications describing the pathogenesis and clinical course of MODS in humans. Providing much of the basis for on‐going research and the development of clinical applications, a consensus statement made by the American College of Chest Physicians and Society of Critical Care Medicine defined parameters that had guided and shaped much of what is known about MODS. Veterinary‐based studies: To date, there are few publications describing MODS in dogs and much of what is known has been derived from case reports and reviews of various critical illnesses in dogs. While a similar syndrome of multiple organ dysfunction likely exists in dogs, a consensus statement defining clinical parameters has not been made. Data sources: Veterinary and human literature review. Conclusions: The development of MODS in human critical illness is widely recognized and major strides have been made in the understanding of this complex syndrome. Scoring schemes applied to human MODS patients have established that with increasing numbers of failing organs, there is a worse prognosis. As a similar finding likely exists in dogs, an awareness of MODS is vital to veterinary critical care clinicians and a consensus definition of MODS in dogs is warranted.