Evaluation of the Effect of Induced Endotoxemia on ROTEM S® and Platelet Parameters in Beagle Dogs Anaesthetized with Sevoflurane

Endotoxemia is thought to induce severe changes in coagulation status. In this study, blood samples from six beagle dogs receiving 1 mg/kg E. coli lipopolysaccharide (LPS) intravenously were analyzed to describe the concurrent changes in platelet count, platelet function assessed with impedance thromboaggregometry, thromboelastometry and d-dimers during artificially induced endotoxemia and its therapy with fluids and vasopressors at five timepoints (baseline, after LPS and 30 mL/kg Ringer’s acetate, during noradrenaline ± dexmedetomidine infusion, after a second fluid bolus and a second time after vasopressors). Results were analyzed for changes over time with the Friedman test, and statistical significance was set at p < 0.05. We found decreased platelet count and function and changes in all platelet-associated rotational thromboelastometry (ROTEM) variables indicating hypocoagulability, as well as increases in d-dimers indicating fibrinolysis within one hour of intravenous administration of LPS, with partial recovery of values after treatment and over time. The fast changes in platelet count, platelet function and ROTEM variables reflect the large impact of endotoxemia on the coagulation system and support repeated evaluation during the progress of endotoxemic diseases. The partial recovery of the variables after initiation of fluid and vasopressor therapy may reflect the positive impact of the currently suggested therapeutic interventions during septic shock in dogs

Evaluation of the ability of haemodynamic variables obtained with minimally invasive techniques to assess fluid responsiveness in endotoxaemic Beagles

Objective: To examine the ability of different haemodynamic variables recorded by minimally invasive monitoring techniques to assess fluid responsiveness (FR) in endotoxaemic Beagles. Study design: Prospective terminal experimental study. Animals: A group of six healthy, purpose-bred Beagle dogs (three intact females and males), age 5–9.8 years (range) and weighing 11.4–17.9 kg. Methods: Endotoxaemic shock was induced by injecting 1 mg kg–1 Escherichia coli lipopolysaccharide (LPS) intravenously in six sevoflurane-anaesthetized mechanically ventilated Beagles for another project. After 10 minutes, three Ringer’s acetate boluses (10 mL kg–1) were administered each over 10 minutes with collection of haemodynamic data immediately before and after each bolus. Thereafter, arterial hypotension was treated with noradrenaline ± dexmedetomidine until arterial pressures increased to a target value. After a wash-out period of 20 minutes another three boluses of fluid were administered and measurements were repeated equally. For each fluid bolus, FR was considered positive when change (Δ) in stroke volume measured by pulmonary artery thermodilution was ≥15%. To test predictive accuracy for FR, we recorded heart rate, invasive arterial, right atrial and pulmonary capillary wedge pressures, pulse wave transit time with haemodynamic monitors, calculated pulse pressure, shock index and rate over pressure evaluation (ROPE) and measured stroke distance and corrected flow time (FTc) with oesophageal Doppler monitoring. Results: A total of 35 measurements (19 positive and 16 negative responses) were evaluated. A FTc < 330 ms, Δ pulse pressure ≥20%, Δ shock index ≤–14% and ΔROPE ≤–17% were the most significant indicators of positive FR with an area under the receiver operating characteristics curve between 0.72 and 0.74. Conclusions and clinical relevance: In endotoxaemic Beagles, none of the assessed haemodynamic variables could predict FR with high sensitivity and specificity

Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophilgelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/ creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage >1; one with anuria and elevated creatinine. Serum creatinine (P 1 versus stage 0, respectively. Endotoxemia induced VAKI stage >1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early

The impact of vatinoxan on microcirculation after intramuscular co-administration with medetomidine in Beagle dogs: a blinded crossover study

Objective: To measure the effects on microcirculation of medetomidine alone (MED) or combined with vatinoxan (MVX). Study design: Randomized, crossover, blinded, experimental study. Animals: A group of eight healthy purpose-bred Beagle dogs. Methods: Each dog was administered 1 mg m–2 MED intramuscularly (IM) or combined with 20 mg m–2 vatinoxan IM (MVX) with a washout period of 7 days. A sidestream dark field (SDF) camera was placed on the buccal mucosa to assess the oral mucosal microcirculation for perfused DeBacker density, proportion of perfused vessels (PPV) (both for all vessels and vessels with a diameter < 20 μm), microvascular flow index (MFI) and heterogeneity index (HI). Videos were recorded at baseline (–5) and 10, 20, 30, 40, 60, 90 and 120 minutes after treatment administration. Linear mixed-effects models were used to assess if microvascular variables were significantly associated with treatment, baseline, and sequence. Results are presented as estimated effect (95% confidence interval), and a p value < 0.05 was considered significant. Results: The interquartile range for baseline measurements was 91.49%–98.42% for PPV, 2.75–3 for MFI and 0–0.36 for HI. Significant effects of treatment and baseline were found. The estimated effect of MED against MVX was –1.98% (–3.53% to –0.42%) for PPV, –0.33 (–0.43 to –0.22) for MFI and 0.14 (0.05 to 0.22) for HI. There were no significant changes seen for perfused DeBacker density, perfused DeBacker density < 20 μm and PPV < 20 μm between treatments. Conclusions and clinical relevance: These results suggest that MVX had significantly fewer effects on buccal mucosal microcirculation than MED. The SDF camera is a useful research tool to assess the microcirculatory status of heavily sedated dogs