Classification of Septic Shock Phenotypes Based on the Presence of Hypotension and Hyperlactatemia in Cats.

Background: Three different phenotypes of septic shock based on changes in blood pressure and lactate are recognized in people. Dysoxic shock, representing the combination of fluid-refractory hypotension and hyperlactatemia, is characterized by greater disease severity and mortality compared to cryptic shock (hyperlactatemia alone) and vasoplegic shock (hypotension with normal blood lactate). Little is known about septic shock and specifically its phenotypes in cats. Objective: To analyze the characteristics and prognostic implications of three septic shock phenotypes in cats with sepsis. Methods: Cats with septic shock were prospectively included. Septic shock was defined by the presence of hypotension (mean blood pressure <60 mmHg) requiring vasopressor support and/or persistent hyperlactatemia (>4 mmol/L) and classified in three subgroups: dysoxic shock, vasoplegic shock and cryptic shock. Clinical and clinicopathological variables including APPLEfast and APPLEfull scores, occurrence of multi-organ dysfunction syndrome (MODS; presence of at least two dysfunctional organs simultaneously) and outcome were compared among subgroups. Cats with sepsis showing normal blood pressure and lactate concentrations hospitalized during the study period were included as uncomplicated sepsis, and compared to cats with septic shock for selected variables. Length of hospital stay and mortality were evaluated in the whole study population. Odds ratios for mortality were calculated using logistic regression analysis. Significance was set at P < 0.05. Results: The study enrolled 48 cats with uncomplicated sepsis and 37 cats with septic shock (dysoxic shock n = 17; vasoplegic shock n = 11; cryptic shock n = 7). Cats with dysoxic shock had significantly higher APPLEfast and APPLEfull scores compared to vasoplegic and cryptic shock. Mortality rates were not significantly different among cryptic (57%), dysoxic (65%) and vasoplegic shock (91%), while MODS occurrence was significantly lower in cats with cryptic shock (57%) compared to patients affected by dysoxic (94%) and vasoplegic (100%) shock. Cats with septic shock had higher frequency of MODS and greater mortality rate than cats with uncomplicated sepsis. Conclusion: Despite similar in-hospital mortality, cats with dysoxic and vasoplegic shock are characterized by having higher occurrence of multi- organ dysfunction compared to cats affected by cryptic shock. Results from this study suggest novel means of identifying high-risk subgroups of septic cats.

Cytokine and Chemokine Profiling in Cats With Sepsis and Septic Shock.

Background: Sepsis is a life-threatening condition associated with an exacerbated production of both pro- and anti-inflammatory cytokines that can promote a hyperactive response to infection or induce immunoparalysis. Data regarding the immune response to sepsis in cats are scarce. Establishing the profiles of cytokines and chemokines in feline sepsis to characterize the nature of the immune responses to sepsis might enable individualized treatments to be developed and targeted. Objective: To evaluate the cytokine and chemokine network in cats with sepsis and septic shock, and to investigate the associations of these analytes with disease severity and outcome. Methods: Blood samples prospectively collected at presentation of cats with sepsis and septic shock to two veterinary teaching hospitals were analyzed. Forty healthy cats were included as controls. A 19-plex feline cytokine/chemokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Cytokine concentrations were compared between groups using the Kruskal-Wallis test with Dunn's post-hoc correction for multiple comparisons. Cytokine concentrations were compared between survivors and non-survivors with the Mann-Whitney U test. Odds ratios were calculated using logistic regression. A multivariable logistic regression model for prediction of septic shock was constructed. Results: The study enrolled 35 septic cats. Many cytokines were undetectable in both sick and healthy control cats and were excluded from subsequent analyses. Comparisons of cytokine concentrations among healthy controls, cats with sepsis (n = 12) and cats with septic shock (n = 23) revealed that sick cats (sepsis or septic shock) had significantly higher plasma concentrations of IL-6, IL-8, KC-like, and RANTES compared to healthy controls. The combination of MCP-1, Flt-3L, and IL-12 was predictive of septic shock. None of the cytokines analyzed was predictive of outcome in this study population. Conclusion: Plasma concentrations of IL-6, IL-8, KC-like, and RANTES are increased in cats with sepsis and may play important roles in pathogenesis. Multivariable modeling suggested that analysis of cytokines might aid differentiation of septic shock from sepsis. None of the cytokines analyzed was predictive of outcome. Measurement of these cytokines might enable future studies to better diagnose and characterize feline sepsis and septic shock.

Multiorgan dysfunction syndrome in feline sepsis: prevalence and prognostic implication.

OBJECTIVES: The current study was designed to evaluate the prevalence and prognostic significance of multiorgan dysfunction syndrome (MODS) in cats with sepsis. METHODS: Cats hospitalised in the intensive care unit of a veterinary university hospital with a diagnosis of sepsis were prospectively enrolled and divided according to disease severity and outcome (survivors; non-survivors). The feline acute patient physiological and laboratory evaluation (APPLE) scores were calculated upon admission, as previously described. Specific criteria to identify selected organ dysfunction (hepatic, renal, respiratory, cardiocirculatory, haemostatic) were adapted from the available human and veterinary literature, and evaluated at baseline and at the end of hospital stay. MODS was defined as the presence of at least two dysfunctional organs simultaneously. Non-parametric statistics were used for comparisons. Univariate and multivariate regression analyses to evaluate significant risk factors for death were carried out. Correlations between variables were assessed by the Spearman's rank correlation coefficient. Significance was set at P <0.05. RESULTS: A total of 43 cats with heterogeneous sources of sepsis were included. MODS was identified in 25/43 cats upon admission and in 32/43 cats at the end of hospital stay. Regression analyses showed a significantly elevated odds ratio for mortality for the presence of MODS, renal and cardiovascular dysfunction upon admission, as well as for the number of dysfunctional organs. The latter was the only variable retained by the model from the multivariate binary logistic regression analysis. Significant correlations were documented between the number of dysfunctional organs and the APPLE scores. CONCLUSIONS AND RELEVANCE: MODS is a frequent complication of feline sepsis, and is associated with worse outcomes. In particular, renal and cardiovascular dysfunction significantly increase the odds for death. Hence, systematic screening for organ dysfunction is advocated in cats with sepsis.