New-onset organ dysfunction as a screening tool for the identification of sepsis and outcome prediction in dogs with systemic inflammation.

Introduction: Sepsis in people is defined as a life-threatening organ dysfunction (OD) caused by a dysregulated host response to infection. In veterinary medicine, sepsis is still defined by the presence of systemic inflammation plus the evidence of infection. Based on recent veterinary studies, multiorgan dysfunction syndrome (MODS) has been associated with a worse outcome in sepsis. Thus, the screening for OD is warranted to identify the most critically ill patients. The aim of this study was to investigate the diagnostic value of new-onset OD for the prediction of sepsis and outcome in a population of critically ill dogs with systemic inflammation. Materials and methods: Dogs admitted to the Emergency Room and/or the Intensive Care Unit with systemic inflammation, defined by a serum C-reactive protein concentration > 1.6 mg/dL, were retrospectively included. Enrolled dogs were categorized according to the presence of sepsis or non-infectious systemic inflammation. The presence of newly diagnosed OD was assessed based on criteria adapted from human literature and previously reported canine criteria. Results: 275 dogs were included: 128 had sepsis and 147 had non-infectious systemic inflammation. The frequency of new-onset OD was not different between these groups. Only the presence of fluid-refractory hypotension was significantly associated with a diagnosis of sepsis (OR 10.51, 3.08-35.94; p < 0.0001). The frequency of at least two ODs was significantly higher in non-survivors compared to survivors, according to both the human and the veterinary criteria considered for the study (p = 0.0001 and p = 0.0004, respectively). Specifically, the presence of acute kidney injury, stupor or coma, prolonged Prothrombin Time and decreased Base Excess were associated with a higher risk of death in the multivariate binary logistic regression. Discussion: In this population of critically ill dogs with systemic inflammation, the detection of newly diagnosed ODs was not able to predict sepsis diagnosis, other than the presence of fluid-refractory hypotension. However, given the strong prognostic significance associated with ODs, our results support the early screening for ODs in any severe inflammatory critical care condition to identify high-risk patients and optimize their management.

Apolipoprotein A1 and serum amyloid A in dogs with sepsis and septic shock.

Introduction: Apolipoprotein-A1 (Apo-A1) acts as a negative acute phase protein (APP) during inflammatory states, and has a potential prognostic value in people and dogs with sepsis. The aim of this retrospective study was to investigate the association of serum Apo-A1 concentration with disease severity, multiorgan dysfunction syndrome (MODS) and outcome in a population of dogs with sepsis, and to assess its correlation with major canine APPs. Methods: Ninety-nine dogs with uncomplicated sepsis (n = 78) or septic shock (n = 21) were included. The serum concentration of Apo-A1, C-reactive protein (CRP) and serum amyloid A (SAA) were recorded, alongside the canine acute patient physiologic and laboratory evaluation fast (APPLEfast) score and the presence of MODS. Results: Dogs with septic shock had significantly lower serum Apo-A1 concentrations (106.3 ± 22.7 mg/dl; reference interval: 123.0-142.3 mg/dl), higher APPLEfast score (30, 13-38) and greater frequency of MODS (67%) compared to those with uncomplicated sepsis (117.9 ± 19.3 mg/dl; 25, 6-33 and 8%, respectively) (P = 0.0201; P = 0.0005; P < 0.0001, respectively). Similarly, dogs with MODS had significantly lower serum Apo-A1 concentrations (104.1 ± 4.6 mg/dl) and higher APPLEfast score values (31, 13-38) compared to those without MODS (118.32 ± 2.1 mg/dl and 26, 6-33, respectively) (P = 0.0050 and P = 0.0038, respectively). Conversely, neither CRP nor SAA were different between these groups. No difference in serum APPs concentrations was detected between survivors and non-survivors. Significant negative correlations were detected between serum Apo-A1 and SAA (P = 0.0056, r = -0.277), and between serum Apo-A1 and the APPLEfast score (P = 0.0027, r = -0.3). In this population, higher values of the APPLEfast score and the presence of MODS were independently associated with a higher risk of death. Discussion: Our study shows that Apo-A1 is a useful biomarker of sepsis severity in dogs, since it is decreased in those with septic shock and MODS. Further prospective investigations are deemed to evaluate the applicability of Apo-A1 to predict sepsis course and response to treatment in septic dogs.

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.

Circulating Methemoblogin Fraction in Dogs With Sepsis.

Large amount of nitric oxide (NO) can be released in patients with sepsis. Methemoglobin is formed from the interaction between NO and hemoglobin. Mild methemoglobinemia reflecting NO overproduction has been reported in septic people, and occasionally associated to septic shock and organ dysfunction. The aim of this retrospective study was to evaluate circulating methemoglobin fraction in dogs with sepsis and to assess its prognostic value. Methemoglobin reference interval (RI) was calculated in 41 healthy dogs and was set at 0-2.2%. A total of 131 dogs with sepsis were included in the study; 24/131 had a circulating methemoglobin ≥2.2%. The median methemoglobin fraction was significantly higher in dogs with sepsis compared to healthy ones (1.7%, 0.4-3.5% vs. 1.0, 0.3-2.2%, P = 0.0005). No significant difference was observed between dogs with uncomplicated sepsis (n = 98) vs. dogs with septic shock (n = 33) (1.8%, 0.4-2.8% vs. 1.5%, 0.4-3.5%, P = 0.74), between dogs with and without multi-organ dysfunction (n = 38 and n = 93, respectively) (1.7%, 0.4-3.5% vs. 1.7%, 0.5-2.8%, P = 0.27), and between survivors (n = 77) vs. non survivors (n = 54) (1.5%, 0.4-2.8% vs. 1.8%, 0.4-3.5%, P = 0.05). Dogs with methemoglobin fraction above or equal to the upper limit of the RI had a significantly higher frequency of death compared to dogs with methemoglobin levels <2.2% (60.0% vs. 36.8%, P = 0.04). In conclusion, mild methemoglobinemia is detected in dogs with sepsis, and methemoglobin values above the RI might be associated with a worse outcome.

Suppression of craving for gamma-hydroxybutyric acid by naltrexone administration: three case reports.

Gamma-hydroxybutyric acid (GHB) is currently used to induce and maintain abstinence from alcohol. Cases of craving and desire to increase doses of GHB have been reported in both clinical trials and nonclinical self-administration. The enhancement of dopamine activity induced by GHB receptor activation might play a role in the euphoric effect and potential craving and the consequent abuse of this drug. Naltrexone (NTX), a mu-opioid antagonist, is effective in inducing and maintaining abstinence from alcohol, reducing relapses in heavy drinking and craving for alcohol in alcohol-dependent outpatients. Taking into account the alcohol antireward property of NTX, we tested its activity in reducing craving for GHB in 3 consecutive cases of alcoholics who manifested craving for this drug. In all patients the combination with NTX suppressed the craving for GHB. The antireward effect of NTX likely results from its interference with the GHB-induced dopamine release, leading to a partial blockade of the GHB reinforcing effect responsible of the craving for the drug. A combined therapy with GHB and NTX seems to be able to suppress craving for the former, thus improving the manageability and safety of treatment.