Computer-controlled closed-loop norepinephrine infusion system for automated control of mean arterial pressure in dogs under isoflurane-induced hypotension: a feasibility study.

Introduction: Intra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system. Methods: NE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane. Results: In the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5-1.5)% to 4 (4-4)% without activating the system, the MAP was lowered from 95 (91-99) to 41 (37-42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0-1.5)% to 4 (4-4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89-95) to 47 (43-49) mmHg but recovered to 58 (57-58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89-100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were - 2.9 (-4.7 to 1.9)%, 2.9 (2.0-4.7)%, 1.3 (0.8-1.8)%, and - 0.24 (-0.34 to -0.11)%·min-1, respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully. Conclusion: This system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs.

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 leukocyte depletion of packed red blood cell units and impact on clinically observed transfusion reactions.

Introduction: The aim of this retrospective study was to determine whether there is an association between leukoreduction of packed red blood cell (pRBC) units and reduction of clinically observed transfusion reactions (TR), particularly febrile non-haemolytic transfusion reactions (FNHTR), and better outcomes in dogs. Secondary aims were to evaluate the effects of other factors suspected to influence transfusion reaction frequency or survival, including crossmatching, use of immunosuppressive drugs, and age and number of the blood products being administered. Materials and methods: Medical data on dogs transfused with leukocyte-reduced (LR) and non-leukocyte-reduced (N-LR) pRBC units at the Animal Hospital Zürich, University of Zürich, Switzerland between January 1, 2007, and December 17, 2018 were searched. Before 2014, only N-LR blood were transfused. After 2014, both LR and N-LR blood were available. Results: A total of 339 canine patients were transfused with 413 pRBC units; 30.5% (126/413) were LR units and 69.5% (287/413) were N-LR. Data collected from medical records was analyzed using univariate and multivariate logistic regression. In the present study, TR occurred in 19.8% of pRBC units (25/126) with LR and in 17.7% (51/287) of pRBC with N-LR; p > 0.05. FNHTR occurred in 6.3% of pRBC units (8/126) with LR and in 4.5% (13/287) of those with N-LR; p > 0.05. There was no correlation between the occurrence of TR and discharge from hospital (p > 0.05). Crossmatching, immunosuppressive therapy, and age of the blood product were not associated with the frequency of TR; p > 0.05 for all. The duration of survival days was not related to the number of transfusions dogs received. Discussion: In the present study, the leukocyte-depletion of transfused pRBC units was not associated with fewer TR nor to fewer FNHTR compared to N-LR units. Discharge of dogs from hospital was not dependent on the occurrence of TR.

Evaluation of cardiovascular effects of intramuscular medetomidine and a medetomidine-vatinoxan combination in Beagle dogs: A randomized blinded crossover laboratory study.

OBJECTIVE: To compare the cardiovascular effects of a combination of medetomidine and vatinoxan (MVX) versus medetomidine (MED) alone administered intramuscularly (IM) and to determine whether heart rate (HR) can be used as a surrogate for cardiac output (CO) after the use of medetomidine with or without vatinoxan. STUDY DESIGN: A randomized, blinded, experimental, crossover study. ANIMALS: A group of eight healthy Beagle dogs aged 4.6 (2.3-9.4) years and weighing 12.9 (9-14.7) kg, median (range). METHODS: Each dog was injected with 1 mg m-2 medetomidine with or without 20 mg m-2 vatinoxan IM with a washout period of 7 days. Cardiovascular data and arterial and mixed venous blood gas samples were collected at baseline, 5, 10, 15, 20, 35, 45, 60, 90 and 120 minutes after treatment administration. CO was measured at all time points via thermodilution. Differences between treatments, period and sequence were evaluated with repeated measures analysis of covariance and the relationship between HR and CO was assessed with a repeated measures analysis of variance; p values < 0.05 were deemed significant. RESULTS: The CO was 47-96% lower after MED than after MVX (p < 0.0001). Increases in systemic, pulmonary arterial and right atrial pressures and oxygen extraction ratio were significantly higher after MED than after MVX (all p < 0.0001). HR was significantly lower after MED and the linear relationship to CO was significant (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Overall, MED affected the cardiovascular system more negatively than MVX, and the difference in cardiovascular function between the treatments can be considered clinically relevant. HR was linearly related to CO, and decreases in HR reflected cardiac performance for dogs sedated with medetomidine with or without vatinoxan.

Atipamezole Reverses Cardiovascular Changes Induced by High-Dose Medetomidine in Cats Undergoing Sedation for Semen Collection.

This study aimed at describing the change in echocardiographic variables after high-dose medetomidine and the reversal with atipamezole in six cats undergoing sedation for semen collection. Further cardiac Troponin I (cTnI) concentration and the effect of repeated sedation were assessed. Echocardiography was performed before and 20 min after sedation with 0.1 mg/kg medetomidine intramuscularly (IM) for urethral catheterisation. Prior to epididymectomy, S-ketamine was administered intravenously. Twenty minutes after reversal with 0.5 mg/kg atipamezole IM, the third echocardiography was performed. Sedation with medetomidine and reversal with atipamezole was repeated on day 7, 14, 21 and 28. Heart rate (HR) and rhythm were monitored throughout all sedations. On day 0 and 28 cTnI concentrations were measured before and after the procedure. After normality testing, the values were compared over time. The administration of medetomidine led to a marked reduction in HR, cardiac output and ventricular systolic function and a significant increase in left ventricular dimensions. Rhythm abnormalities, such as ventricular premature complexes and idioventricular rhythm, could be observed. The administration of atipamezole completely reversed sedation and the changes in haemodynamic variables. No significant increase in cTnI concentrations could be detected, although two out of six cats showed values above the reference range.

Evaluation of the Analgesic Efficacy of Undiluted Intraperitoneal and Incisional Ropivacaine for Postoperative Analgesia in Dogs after Major Abdominal Surgery.

Recommendations for intraperitoneal (IP) and incisional (INC) administration of local anaesthetics after visceral surgery exist, but evidence is scarce. This prospective, randomized, blinded, controlled, clinical trial compared postoperative pain in dogs undergoing major abdominal surgery. Sixteen client-owned dogs were anaesthetized with a standardized balanced protocol including opioids and received either 2 mg/kg ropivacaine IP (0.27 mL/kg) and a 1 mg/kg INC splash (0.13 mL/kg) or equal volumes of saline. Influence of the treatment on heart rate (HR) and postoperative pain was assessed using the Short Form of the Glasgow Composite Pain Scale (GCPS-SF), a dynamic interactive visual analogue scale (DIVAS) and mechanical nociceptive threshold testing (MNT). Data was tested with mixed ordinal regression and log linear mixed models for 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h after extubation. Rescue analgesia was given to 3/8 dogs after ropivacaine and 0/8 dogs after saline. GCPS-SF and MNT were not different between groups. DIVAS was slightly higher after ropivacaine (odds increased by 5.44 (confidence interval (CI) 1.17-9.96, p = 0.012)), and HR after ropivacaine was 0.76 * that after saline (CI 0.61-0.96, p = 0.02) with no effect of time (p = 0.1). Undiluted ropivacaine IP and INC was not beneficial for postoperative analgesia.

Epididymectomy as a novel surgical procedure; application in the domestic cat.

Feline overpopulation raises issues concerning health, ecology, economy, and ethics. Procedures to limit overpopulation should carefully address animal welfare, efficiency, costs, and feasibility. Vasectomy in unowned cats is suggested as preferable to standard neutering as it maintains male sexual behaviour which may induce ovulation and pseudopregnancy in intact females and may prevent immigration of other males. Vasectomy is not performed routinely because it is fastidious, time consuming and requires more material than standard neutering. We describe epididymectomy as an alternative. In a first experiment, we analysed semen, testosterone, behaviour and pain in six experimental cats before and after epididymectomy, and after castration two months later. Excised tissues were analysed histologically. Testosterone concentrations did not differ significantly between intact and epididymectomised animals but were significantly different after castration. Sexual behaviour and testicular spermatogenesis persisted after epididymectomy, but with a marked drop in the semen count after 7 days. The Glasgow pain scores did not differ significantly after epididymectomy and castration. In a subsequent experiment, 20 privately owned cats were epididymectomised and castrated immediately afterwards, to analyse the learning curve and perioperative complications. The time required for an epididymectomy was significantly shorter than for castration. The study confirms that epididymectomy is quicker and less invasive than castration, it is associated with minimal risks and post-operative pain while easy to learn and inexpensive. Further field studies are required to test its efficiency for feline feral population control or in other species such as in bears, lions or deer, where infertility is required and castration not wanted.

Development and comparison of an esophageal Doppler monitoring-based treatment algorithm with a heart rate and blood pressure-based treatment algorithm for goal-directed fluid therapy in anesthetized dogs: A pilot study.

The objective of this pilot study was to determine the feasibility of a study comparing the efficacy of an esophageal Doppler monitor (EDM)-based fluid therapy algorithm with a heart rate (HR)- and mean arterial blood pressure (MAP)-based algorithm in reducing hypotension and fluid load in anesthetized dogs. Client-owned dogs undergoing general anesthesia for surgical procedures were randomized to two groups. An EDM probe for monitoring blood flow in the descending aorta was placed in each dog before receiving a crystalloid bolus (5 mL/kg) over 5 min. Fluids were repeated in case of fluid responsiveness defined by increasing Velocity Time Integral (VTI) ≥ 10% in group EDM and by decreasing HR ≥ 5 beats/min and/or increasing MAP ≥ 3 mmHg in group standard. The feasibility outcomes included the proportion of dogs completing the study and the clinical applicability of the algorithms. The clinical outcomes were the total administered fluid volume and the duration of hypotension defined as MAP < 60 mmHg. Data was compared between groups with Mann-Whitney U-test. p < 0.05 were deemed significant. Of 25 dogs screened, 14 completed the study (56%). There were no differences in the proportion of recorded time spent in hypotension in group standard [2 (0-39)% (median (range))] and EDM [0 (0-63) %, p = 1], or the total volume of fluids [standard 8 (5-14) mL/kg/h, EDM 11 (4-20) mL/kg/h, p = 0.3]. This study declined the feasibility of a study comparing the impact of two newly developed fluid therapy algorithms on hypotension and fluid load in their current form. Clinical outcome analyses were underpowered and no differences in treatment efficacy between the groups could be determined. The conclusions drawn from this pilot study provide important information for future study designs.

Evaluation of the Effect of Storage Time on ROTEM S® Parameters in Healthy and Ill Dogs.

Viscoelastic testing as a bedside test to assess global haemostasis has gained popularity in the past decade, with rotational thromboelastometry (ROTEM) and thromboelastography (TEG) being the two commonly used devices. TEG studies suggest analysis 30 min after blood sampling. However, the reproducibility of results over time for ROTEM analysis using lyophilized samples in dogs has not been established. In this study, we investigated the influence of time on viscoelastic testing, using 33 healthy staff-/client-owned dogs for blood sampling and repeated measurements of ROTEM tracings at three different time points after blood collection. Additionally, a group of 21 hospitalized patients with suspected coagulation disorders were included to investigate whether stability over time was comparable between healthy and ill dogs. We demonstrated a significant difference of ROTEM tracings over time, with a tendency towards hypocoagulability over time. These changes do have a clinical relevance as they exceed reference intervals and could therefore lead to erroneous conclusions about a patient's coagulation status. Therefore, time-specific reference intervals are proposed and presented in this publication.

Effects of acepromazine and dexmedetomidine, followed by propofol induction and maintenance with isoflurane anaesthesia, on the microcirculation of Beagle dogs evaluated by sidestream dark field imaging: an experimental trial.

OBJECTIVE: To investigate the effects of intramuscularly administered acepromazine or dexmedetomidine on buccal mucosa microcirculation in Beagle dogs. STUDY DESIGN: Experimental, blinded, crossover study. ANIMALS: A group of seven Beagle dogs aged 7.5 ± 1.4 years (mean ± standard deviation). METHODS: Microcirculation was assessed on buccal mucosa using sidestream dark field videomicroscopy. After baseline measurements, 5 µg kg-1 dexmedetomidine or 30 µg kg-1 acepromazine were administered intramuscularly. After 10, 20 and 30 minutes, measurements were repeated. At 40 minutes after premedication, anaesthesia was induced with propofol intravenously and maintained with isoflurane. Measurements were repeated 50, 60 and 65 minutes after the injection of the investigated drugs. Analysed microcirculatory variables were: Perfused de Backer density, Perfused de Backer density of vessels < 20 µm, Proportion of perfused vessels and Proportion of perfused vessels < 20 µm. Heart rate (HR), systolic, diastolic (DAP) and mean (MAP) arterial pressures were recorded at the same time points. Macro- and microcirculatory variables were analysed using a linear mixed model with baseline as a covariate, treatment, trial period and repetition as fixed effects and time and dog as random effect. Results are presented as effect size and confidence interval; p values < 0.05 were considered significant. RESULTS: After acepromazine, Perfused de Backer density was greater during sedation and anaesthesia [3.71 (1.93-5.48 mm mm-2, p < 0.0001) and 2.3 (0.86-3.75 mm mm-2, p < 0.003)], respectively, than after dexmedetomidine. HR was significantly lower, whereas MAP and DAP were significantly higher with dexmedetomidine during sedation and anaesthesia (p < 0.0001 for all) compared with acepromazine. CONCLUSIONS AND CLINICAL RELEVANCE: The sedative drugs tested exerted a significant effect on buccal mucosal microcirculation with a higher Perfused de Backer density after the administration of acepromazine compared with dexmedetomidine. This should be considered when microcirculation is evaluated using these drugs.

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 given 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.

Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy?

Introduction: In recent years ketamine has increasingly become the focus of multimodal emergency management for epileptic seizures. However, little is known about the effect of ketamine on brain metabolites in epileptic patients. Magnetic resonance spectroscopy (MRS) is a non-invasive technique to estimate brain metabolites in vivo. Our aim was to measure the effect of ketamine on thalamic metabolites in idiopathic epileptic (IE) dogs using 3 Tesla MRS. We hypothesized that ketamine would increase the glutamine-glutamate (GLX)/creatine ratio in epileptic dogs with and without antiseizure drug treatment, but not in control dogs. Furthermore, we hypothesized that no different responses after ketamine administration in other measured brain metabolite ratios between the different groups would be detected. Methods: In this controlled prospective experimental trial IE dogs with or without antiseizure drug treatment and healthy client-owned relatives of the breeds Border Collie and Greater Swiss Mountain Dog, were included. After sedation with butorphanol, induction with propofol and maintenance with sevoflurane in oxygen and air, a single voxel MRS at the level of the thalamus was performed before and 2 min after intravenous administration of 1 mg/kg ketamine. An automated data processing spectral fitting linear combination model algorithm was used to estimate all commonly measured metabolite ratios. A mixed ANOVA with the independent variables ketamine administration and group allocation was performed for all measured metabolites. A p < 0.05 was considered statistically significant. Results: Twelve healthy control dogs, 10 untreated IE and 12 treated IE dogs were included. No significant effects for GLX/creatine were found. However, increased glucose/creatine ratios were found (p < 0.001) with no effect of group allocation. Furthermore, increases in the GABA/creatine ratio were found in IEU dogs. Discussion: MRS was able to detect changes in metabolite/creatine ratios after intravenous administration of 1 mg/kg ketamine in dogs and no evidence was found that excitatory effects are induced in the thalamus. Although it is beyond the scope of this study to investigate the antiseizure potential of ketamine in dogs, results of this research suggest that the effect of ketamine on the brain metabolites could be dependent on the concentrations of brain metabolites before administration.

Whole blood platelet impedance aggregometry with the ROTEM platelet device: comparison of 2 anticoagulants and storage times for the establishment of canine reference intervals.

The ROTEM platelet device, a point-of-care whole blood platelet impedance aggregometer, is an add-on to the rotational thromboelastometry ROTEM delta device. The latter has been validated in dogs. We examined whether canine whole blood is suited for analysis with the ROTEM platelet device using adenosine-5'-diphosphate (ADP) and arachidonic acid (ARA) as agonists for platelet activation, and if there are significant differences between sample storage times and anticoagulants used. Subsequently, we determined canine reference intervals (RIs) for the ROTEM platelet device for ADP and ARA. In a pilot study, we examined whole blood from 7 dogs after 15-min and 60-min storage of lithium-heparinized samples and 40-min and 80-min storage of hirudinized samples. Statistical analysis showed no significant differences between ROTEM platelet device results for both ADP and ARA in lithium-heparin and hirudin anticoagulated canine whole blood. Lithium-heparinized blood samples analyzed after 15-min storage had the lowest coefficient of variation. RIs were determined for heparinized whole blood samples from 49 dogs after 15 min of storage.

Coagulation Status in Dogs Naturally Infected with Angiostrongylus vasorum.

Angiostrongylus vasorum infection has been associated with coagulopathies including hyperfibrinolysis. We compared coagulation status including thromboelastometry (ROTEM) parameters in dogs naturally infected with A. vasorum versus healthy dogs to determine clinicopathological parameters associated with bleeding, hypocoagulopathy, and hyperfibrinolysis. Clinical signs, white blood cell count, platelet count, hematocrit, plasmatic coagulation tests (PT, aPTT, fibrinogen concentration), D-dimer, and ROTEM S parameters (Ex-tem, In-tem, Fib-tem, Ap-tem) were analysed and compared between bleeding, nonbleeding, and control dogs and between hypo- and normocoagulable animals. Clinical signs of bleeding were present in 6/9 (67%) hypocoagulable and 1/9 (11%) normocoagulable dogs. PT, fibrinogen concentration, and several ROTEM parameters were significantly different between hypocoagulable and normocoagulabe A. vasorum infected dogs. Hyperfibrinolysis was identified in 44% of infected dogs and was significantly more common in bleeding and hypocoagulable dogs. Hyperfibrinolysis was significantly associated with low MCFFib-tem but not with low fibrinogen concentration or increased D-dimers. CFTEx-tem > 248 swas 100% sensitive and 89% specific to predict hyperfibrinolysis. Hyperfibrinolysis, hypocoagulability and bleeding are common in A. vasorum infected dogs. Only Ex-tem and Fib-tem parameters and potentially PT were associated with bleeding or hypocoagulability. Ex-tem analysis enables detection of bleeding, hypocoagulability and hyperfibrinolysis within minutes.

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-1Escherichia 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.

Impact of general anesthesia on rotational thromboelastometry (ROTEM) parameters and standard plasmatic coagulation tests in healthy Beagle dogs.

OBJECTIVE: To assess the influence of general anesthesia on rotational thromboelastometry (ROTEM) and standard coagulation testing in healthy dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: 10 healthy Beagle dogs. METHODS: Dogs were administered methadone (0.2 mg/kg) intramuscularly. Anesthesia was co-induced intravenously 30 min later with midazolam (0.1 mg/kg) and propofol to effect, and maintained with sevoflurane. Crystalloids were administered at 5 ml/kg/h. Blood was sampled by direct venipuncture before induction (T0) and 3.5 h later (T3.5) and ROTEM parameters (ExTEM, InTEM, FibTEM, ApTEM), standard plasmatic coagulation tests (prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration), hematology, ionized calcium, triglycerides, pH, lactate and body temperature were compared over time with Students t - test or Wilcoxon matched pairs signed-rank tests. RESULTS: The following variables dropped significantly between T0 and T3.5: body temperature (p < 0.0001), hematocrit (p < 0.0001), platelet count (p < 0.01), pH (p < 0.01), triglycerides (p < 0.01), fibrinogen concentration (p < 0.01), ExTEM, FibTEM (p < 0.01) and ApTEM (p < 0.05) clotting times. Lactate concentration (p < 0.01), aPTT (p < 0.05) and FibTEM maximum clot firmness increased (p < 0.05). No changes were noted in ionized calcium, PT and InTEM values. CONCLUSION AND CLINICAL RELEVANCE: General anesthesia with concurrent hemodilution and hypothermia induced significant but clinically irrelevant changes in coagulation variables measured at 37 °Celsius. Blood samples from anaesthetized animals can be used for determination of coagulation status in dogs.

Prospective, controlled, blinded, randomized crossover trial evaluating the effect of maropitant versus ondansetron on inhibiting tranexamic acid-evoked emesis.

OBJECTIVE: To evaluate the incidence of tranexamic acid (TXA)-induced nausea and vomiting after the prophylactic use of 2 antiemetics, ondansetron and maropitant, compared with saline. DESIGN: Prospective, blinded, placebo-controlled, randomized, crossover study. SETTING: University research facility. ANIMALS: Eight adult, purpose-bred Beagles. INTERVENTION: Dogs received 3 treatments on 3 occasions with a 3-week washout period. Either maropitant (1 mg/kg), ondansetron (0.2 mg/kg), or saline solution was given intravenously in equal volumes, followed 10 minutes later by 50 mg/kg IV TXA. A blinded observer evaluated the dogs for signs of vomiting and nausea for 30 minutes. The severity of nausea was assessed with a visual analog scale (VAS) and recorded at baseline before TXA, and at the end of 3 observational periods: 0-5, 5-15, and 15-30 minutes after TXA. A generalized linear mixed effect model was used to assess for group and period effects. Statistical significance was set at P < 0.05 . MEASUREMENTS AND MAIN RESULTS: None of the dogs vomited after maropitant. Emesis occurred in 5 out of 8 dogs (62.5%), a median (range) of 1 time (1-2) after ondansetron and 1 time (1-3) after saline. There was a significant effect on vomiting of maropitant against saline (P < 0.0001) but not for ondansetron against saline (P = 0.53). The highest nausea VASs were recorded during the first 5 minutes after TXA with a significant reduction of VAS variability in the maropitant group (P = 0.003). The effect of maropitant and ondansetron against saline on the severity of nausea was not statistically significant (P = 0.069). CONCLUSION: The neurokinin 1 receptor antagonist maropitant at the dose used, administered IV 10 minutes before 50 mg/kg TXA, was effective in preventing vomiting compared with ondansetron and placebo. Our results support the prophylactic IV administration of maropitant in dogs that are scheduled to receive TXA.

Pharmacokinetics of S-ketamine and R-ketamine and their active metabolites after racemic ketamine or S-ketamine intravenous administration in dogs sedated with medetomidine.

OBJECTIVE: To assess the differences in the pharmacokinetic profiles of S-ketamine, R-ketamine and their metabolites, S-norketamine and R-norketamine, and to measure relevant physiologic variables after intravenous administration of racemic (RS) ketamine or S-ketamine alone in Beagle dogs sedated with medetomidine. STUDY DESIGN: Experimental, blinded and randomized crossover study. ANIMALS: A total of six (three female and three male) adult Beagle dogs. METHODS: Medetomidine (450 µg m-2) was administered intramuscularly, followed by either S-ketamine (2 mg kg-1) or RS-ketamine (4 mg kg-1) 20 minutes later, both administered intravenously. Blood samples were collected before medetomidine administration and at multiple time points 1-900 minutes following the ketamine administration. Plasma samples were analysed using liquid chromatography-tandem mass spectrometry. Heart rate, respiratory rate, noninvasive blood pressure, haemoglobin saturation with oxygen and body temperature were measured at baseline, before ketamine administration, and 1, 2, 5, 10, 15, 20 and 30 minutes after ketamine administration. All cardiovascular variables, blood glucose, haemoglobin and lactate concentrations were analysed using different linear mixed effects models; the significance was set at p < 0.05. RESULTS: S-ketamine showed a two-compartment kinetic profile; no statistically significant differences were observed between its concentrations or in the calculated pharmacokinetic parameters following S- or RS-ketamine. When the racemic mixture was administered, no differences were detected between R- and S-ketamine concentrations, but the area under the curve (AUC) for R-norketamine was significantly lower than that for S-norketamine. Clinically relevant physiologic variables did not show statistically significant differences following the administration of the racemic mixture or of S-ketamine alone. CONCLUSIONS AND CLINICAL RELEVANCE: This study performed in dogs showed that RS-ketamine and S-ketamine combined with medetomidine showed enantioselective pharmacokinetics as S- and R-norketamine AUCs were different, but S-ketamine levels were identical.

Correlation of rotational thromboelastometry (ROTEM) parameters with platelet count and their ability to predict thrombocytopenia in dogs.

The study objectivs were to evaluate the correlation between platelet count (PLT) and rotational thromboelastometry (ROTEM) parameters and to determine ROTEM cut-off values for identification of thrombocytopenia in dogs. Medical records of 113 dogs with concurrent EXTEM (ROTEM activated by proprietary tissue factor), FIBTEM (EXTEM with added cytochalasin D) analysis and PLT were retrospectively reviewed. Signalment, treatment prior to analysis, hematocrit (HCT), EXTEM/FIBTEM maximum clot firmness (MCFEXTEM, MCFFIBTEM), EXTEM/FIBTEM maximum clot elasticity (MCEEXTEM, MCEFIBTEM) and EXTEM maximum lysis (MLEXTEM) were extracted from patient records and ROTEM database. Delta (Δ) MCF was calculated as MCFEXTEM-MCFFIBTEM and ΔMCE as MCEEXTEM-MCEFIBTEM. The PLT was correlated to MCFEXTEM, MCEEXTEM, ΔMCF and ΔMCE using Spearman-Rho analysis. Correlations were further analyzed in thrombocytopenic dogs. The ability to predict thrombocytopenia was evaluated with receiver operating characteristics (ROC). Thirty-seven samples (32.7%) showed thrombocytopenia (<130 × 109/L) and 19 samples (17%) severe thrombocytopenia (<60* x 109/L). The PLT significantly correlated with MCFEXTEM (r = 0.545, P < .001), MCEEXTEM (r = 0.547, P < .001), ΔMCF (r = 0.441, P < .001) and ΔMCE (r = 0.559, P < .001). MCFEXTEM < 49 mm, MCEEXTEM < 93, ΔMCF <42 mm and ΔMCE <90 predicted thrombocytopenia <60 × 109/L with a sensitivity of 90% and a specificity of 78% with a negative predictive value >97% for all 4 parameters. In conclusion, PLT in dogs correlated moderately but significantly with all evaluated ROTEM parameters. All parameters were able to rule out thrombocytopenia <60 × 109/L with a high negative predictive value, while the sensitivity to predict thrombocytopenia was only moderate and the positive predictive value was low.