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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., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Objectives The aim of this study was to determine in-house reference intervals (RIs) for venous blood analysis with the RAPIDPoint 500 blood gas analyser using blood gas syringes (BGSs) and to determine whether immediate analysis of venous blood collected into lithium heparin (LH) tubes can replace anaerobic blood sampling into BGSs. Methods Venous blood was collected from 24 healthy cats and directly transferred into a BGS and an LH tube. The BGS was immediately analysed on the RAPIDPoint 500 followed by the LH tube. The BGSs and LH tubes were compared using paired t-test or Wilcoxon matched-pairs signed-rank test, Bland-Altman and Passing-Bablok analysis. To assess clinical relevance, bias or percentage bias between BGSs and LH tubes was compared with the allowable total error (TEa) recommended for the respective parameter. Results Based on the values obtained from the BGSs, RIs were calculated for the evaluated parameters, including blood gases, electrolytes, glucose and lactate. Values derived from LH tubes showed no significant difference for standard bicarbonate, whole blood base excess, haematocrit, total haemoglobin, sodium, potassium, chloride, glucose and lactate, while pH, partial pressure of carbon dioxide and oxygen, actual bicarbonate, extracellular base excess, ionised calcium and anion gap were significantly different to the samples collected in BGSs ( P <0.05). Furthermore, pH, partial pressure of carbon dioxide and oxygen, extracellular base excess, ionised calcium and anion gap exceeded the recommended TEa. Conclusions and relevance Assessment of actual and standard bicarbonate, whole blood base excess, haematocrit, total haemoglobin, sodium, potassium, chloride, glucose and lactate can be made based on blood collected in LH tubes and analysed within 5 mins. For pH, partial pressure of carbon dioxide and oxygen, extracellular base excess, anion gap and ionised calcium the clinically relevant alterations have to be considered if analysed in LH tubes.

The aims of this study were to measure plasma levels of R- and S-ketamine and their major metabolites R- and S-norketamine following single intravenous bolus administration of racemic or S-ketamine in sevoflurane anaesthetised dogs and to calculate the relevant pharmacokinetic profiles. Six adult healthy beagle dogs were used in the study. An intravenous bolus of 4mg/kg racemic ketamine (RS-KET) or 2mg/kg S-ketamine (S-KET) was administered, with a three-weeks washout period between treatments. Venous blood samples were collected at fixed times until 900min and R- and S-ketamine as well as R- and S-norketamine plasma levels determined by liquid chromatography coupled with tandem mass spectrometry. Cardiovascular parameters were recorded during the anaesthesia until 240min. All dogs recovered well from anaesthesia. No statistical differences between groups were detected in any cardiovascular parameter. The pharmacokinetics of S-ketamine did not differ when injected intravenously alone or as part of the racemic mixture in dogs anaesthetised with sevoflurane. Following racemic ketamine, the area under the curve of R-norketamine was statistically higher than the one of S-norketamine., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To establish reference intervals for rotational thromboelastometry (ROTEM) using feline blood., Design: Prospective study., Setting: University teaching hospital., Animals: Twenty-three clinically healthy cats between 1 and 15 years., Intervention: For each cat, whole blood was collected via jugular or medial saphenous venipuncture, and blood was placed into a serum tube, a tube containing potassium-EDTA, and tubes containing 3.2% sodium citrate. The tubes were maintained at 37°C for a maximum of 30 minutes before coagulation testing., Measurements and Main Results: ROTEM tests included the EXTEM, INTEM, FIBTEM, and APTEM assays. In addition, prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration (Clauss method) were analyzed for each cat. Reference intervals for ROTEM were calculated using the 2.5-97.5 th percentile for each parameter, and correlation with the standard coagulation profile was performed. Compared to people, clinically healthy cats had similar values for the EXTEM and INTEM assays, but had lower plasma fibrinogen concentrations (0.9-2.2 g/L), resulting in weaker maximum clot firmness (MCF, 3-10 mm) in the FIBTEM test. In 18 cats, maximum lysis (ML) values in the APTEM test were higher than in the EXTEM test, which seems unlikely to have occurred in the presence of aprotinin. It is possible that the observed high maximum lysis values were due to clot retraction rather than true clot lysis. Further studies will be required to test this hypothesis., Conclusions: Cats have a weaker clot in the FIBTEM test, but have a similar clot strength to human blood in the other ROTEM assays, which may be due to a stronger contribution of platelets compared to that found in people. In cats, careful interpretation of the results to diagnose hyperfibrinolysis is advised, especially with the APTEM test, until further data are available., (© Veterinary Emergency and Critical Care Society 2017.)

This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and received morphine intramuscularly. The sciatic and femoral nerves of the leg to be operated on were located using a nerve stimulator (1 Hz, 0.5 mA). Rabbits were assigned to a treatment group (LB; n = 12) or a placebo group (P; n = 12) in a randomized blinded fashion. Group LB received lidocaine 2% (1 mg/kg) combined with bupivacaine 0.5% (0.25 mg/kg) injections around the sciatic and femoral nerves (0.1 mL/kg total volume per site) and subcutaneous infiltration of the incision site with lidocaine 1% (1.25 mg/kg). Group P received the same volume of 0.9% NaCl. Rabbits in group P required higher doses of intraoperative fentanyl and propofol to reduce heart rate and suppress increase in systolic blood pressure, and maintain an adequate anaesthetic plane. Interventional analgesia (buprenorphine and carprofen) was required significantly earlier in rabbits in group P (2 and 6 h after the first nerve blockade, respectively) based on assessment of their pain-related behaviour and range of motion. Using a visual analogue scale (0 mm= no pain to 100 mm= maximal possible pain), rabbits in group LB were judged to show significantly less pain compared with rabbits in group P (14 ± 10 mm and 37 ± 25 mm, respectively) 2 h after nerve blockade. In conclusion, this technique of perineural analgesia combined with incision site infiltration reduced intraoperative fentanyl requirements and improved postoperative analgesia in rabbits.

Objectives: To evaluate cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane receiving medetomidine or S-ketamine infusions., Study Design: Randomized, blinded, prospective clinical trial., Animals: Fifty horses undergoing elective surgery., Methods: After acepromazine and flunixin meglumine premedication, horses received medetomidine (7 μg kg -1 ) intravenously (IV). Anaesthesia was induced with midazolam and racemic ketamine (Med treatment group; 2.2 mg kg -1 ; n = 25) or S-ketamine (S-ket treatment group; 1.1 mg kg -1 ; n = 25) IV and maintained with isoflurane in oxygen/air and medetomidine (Med; 3.5 μg kg -1 hour -1 ) or S-ketamine (S-ket; 0.5 mg kg -1 hour -1 ). All horses were mechanically ventilated. Cardiopulmonary variables were evaluated. Isoflurane end-tidal concentrations (Fe'Iso), dobutamine requirements and thiopental boli were recorded. Plasma samples were collected in six horses to evaluate S-ketamine and S-norketamine concentrations. After surgery, medetomidine 2 μg kg -1 was administered IV. Four independent observers scored recovery using a visual analogue scale and a numerical rating scale., Results: Both groups required similar mean Fe'Iso (1%). However, S-ket horses needed more thiopental boli. Median intraoperative cardiac index values were higher with S-ket (4.5 L minute -1  m -2 ) than Med (3.9 L minute -1  m -2 ). Overall, there were no differences in heart rate, blood pressure or dobutamine requirements; however, horses in S-ket showed higher heart rate values at 30 minutes after anaesthesia induction. Compared with Med horses, S-ket horses showed decreased PaO 2 and increased pulmonary venous admixture values estimated with the Fshunt calculation. Recoveries were shorter and of poorer quality with S-ket. During infusion, S-ketamine and S-norketamine plasma concentrations lay in the ranges of 0.209-0.917 μg mL -1 and 0.250-0.723 μg mL -1 , respectively., Conclusions and Clinical Relevance: Despite the higher intraoperative cardiac index with S-ket, both protocols were considered to provide acceptable cardiovascular function. However, recovery quality was significantly better in the Med group., (© 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To assess agreement and trending ability of transpulmonary thermodilution (TPTD), calibrated pulse contour (PiCCO), and pulse power (PulseCO) methods compared to pulmonary artery thermodilution (PATD) for determination of cardiac output (CO) in anesthetized dogs., Design: Experimental, prospective study., Setting: University teaching hospital., Animals: Six adult Beagle dogs., Interventions: Dogs were anesthetized with sevoflurane and instrumented with pulmonary and femoral artery thermodilution catheters. CO was measured at baseline and at 5, 15, 30, 45, 60, 120, 180, and 240 minutes after IV administration of ketamine or s-ketamine. Baseline PATD and TPTD calibrated PulseCO and PiCCO, respectively. Agreement and trending ability was analyzed with Bland-Altman, concordance, and polar plot methodology., Measurements and Main Results: Median (range) CO values of 2.27 (0.98-3.4) L/min were measured with PATD, and 2.8 (1.9-4.04) L/min with TPTD, which resulted in a mean bias (± standard deviation) of -0.66 (± 0.36) L/min. Concordance rate was 91% and radial limits of agreement (RLOA) were ±35°. PATD against PiCCO resulted in a mean bias of -0.71 (± 0.62) L/min and PATD against PulseCO in a mean bias of 0.13 (± 0.46) L/min. The continuous techniques resulted in concordance rates of 77% for PATD-PiCCO and 74% for PATD-PulseCO and RLOA of ±57° and ±60°, respectively., Conclusions: Intermittent TPTD showed marginal trending ability, while continuous pulse contour and pulse power methods showed poor trending ability over a 4-hour period. The poor performance and possible side effects of the methods tested in this study suggest that they should not be recommended for use in critical patients., (© Veterinary Emergency and Critical Care Society 2016.)

Objective: To evaluate the non-calibrated, minimally invasive cardiac output (CO) monitor FloTrac/Vigileo (FloTrac) against thermodilution (TD) CO in standing horses., Study Design: Prospective, experimental trial., Animals: Nine adult horses weighing a median (range) of 535 (470-602) kg., Methods: Catheters were placed in the right atrium, pulmonary artery and carotid artery under local anaesthesia. CO was measured 147 times by TD and FloTrac and indexed to body weight. Changes in CO were achieved with romifidine or xylazine and dobutamine constant rate infusions. Bland-Altman analysis, concordance and polar plot analysis were used to assess agreement and ability to track changes in CO., Results: Mean ± standard deviation COTD of 48 ± 16 mL kg(-1) minute(-1) (range: 19-93 mL kg(-1) minute(-1) ) and mean COF loTrac of 9 ± 3 mL kg(-1) minute(-1) (range: 5-21 mL kg(-1) minute(-1) ) were measured. Low agreement with a large mean bias of 39 mL kg(-1) minute(-1) and wide limits of agreement of 8-70 mL kg(-1) minute(-1) were found. The percentage error of 108% and precision of TD of ± 18% resulted in an estimated precision of FloTrac of ± 106%. Comparison of changes in COF loTrac with changes in COTD gave a concordance rate of 52% in the four-quadrant plot, and a mean polar angle of -11° with radial limits of agreement of ± 61 ° in the polar plot. Mean arterial pressure (MAP) and COF loTrac were positively correlated (r = 0.5, p < 0.0001). No correlation of MAP with COTD was observed., Conclusions and Clinical Relevance: The FloTrac system, originally designed for use in humans, neither measured absolute CO in standing horses accurately nor tracked relative changes in CO measured by TD correctly. The false dependence of COF loTrac on arterial blood pressure further discourages the use of this technique in horses., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To compare the agreement, repeatability and trending ability of transpulmonary thermodilution (TPTD) and pulmonary artery thermodilution (PATD) cardiac output (Q˙t) measurements in unsedated newborn calves., Study Design: Prospective experimental trial., Animals: Eight newborn calves weighing a median (range) of 53 (46-59) kg., Methods: Pulmonary and femoral artery thermodilution catheters were placed under local anaesthesia. A total of 382 PATD and TPTD Q˙t measurements were performed simultaneously. Cardiac output was influenced by intravenous doxapram and theophylline in a randomized crossover fashion. Bland-Altman analysis for multiple comparisons, concordance and polar plots were used to assess TPTD against PATD., Results: Median (range) cardiac index values measured with PATD and TPTD were 197 mL kg(-1) minute(-1) (74-335 mL kg(-1) minute(-1)) and 196 mL kg(-1) minute(-1) (59-395 mL kg(-1) minute(-1)), respec-tively. A small mean bias of -3 mL kg(-1) minute(-1) with limits of agreement (LOA) of -64 to 58 mL kg(-1) minute(-1) and a percentage error of 31% were found. Eighty-two mean values were calculated. This reduced the LOA to -50 to 41 mL kg(-1) minute(-1) with a similar small bias and a percentage error of 23%. Mean TPTD tracked changes in Q˙t compared with mean PATD with 90% concordance, a mean polar angle of 6° and radial LOA of 43°, indicating marginal trending ability. Keeping the femoral artery catheter patent and obtaining acceptable measurements were very challenging because the calves were not used to being restrained. Calf movement had less influence on PATD., Conclusions and Clinical Relevance: We recommend that PATD remains the reference method to measure Q˙t in unsedated newborn calves. However, the robust results of the evaluation of the less invasive TPTD technique warrants further evaluation taking into account the difficulties reported in this study., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

The present study evaluated transpulmonary thermodilution (TPTD) and pulse contour cardiac output (PCCO) both measured by the PiCCO Plus™ monitor (Pulsion Medical Systems, Munich, Germany) against pulmonary artery thermodilution (PATD) in cats as a hemodynamic model for small children. A wide range of cardiac outputs (CO) was simultaneously measured. Accuracy and trending abilities were critically evaluated. Three cats were studied under isoflurane anesthesia and 160 CO measurements were performed with 3 mL ice-cold 5 % dextrose with PATD and TPTD. The results were compared with the PCCO measurement before the bolus measurement. Cardiac output was manipulated from 32 to 224 mL/kg/min by dobutamine, dopamine, phenylephrine, medetomidine and increased concentrations of isoflurane. Bland-Altman analysis, concordance and polar plot analysis were performed to assess accuracy and trending ability. TPTD was measuring constantly higher than PATD with a mean bias of 73 mL/kg/min and limits of agreement of 34-112 mL/kg/min, a concordance rate of 94 % and a mean polar angle of -5° with radial limits of agreement (RLOA) of 33°. Concordance rate of the PCCO versus PATD was 82 % with a mean polar angle of -10° and RLOA of 46° and versus TPTD 90 % with a mean polar angle of -6° and RLOA of 46°. Both tested methods constantly overestimated simultaneous PATD measurements. The small size, low flows and the relative short catheter not reaching the abdominal aorta may explain that. However TPTD tracked changes accurately opposed to a poor trending ability of the PCCO measurement.

The aim of this study was to test the effect of cardiac output (CO) and pulmonary artery hypertension (PHT) on volumetric capnography (VCap) derived-variables. Nine pigs were mechanically ventilated using fixed ventilatory settings. Two steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO was increased by 50% from baseline (COup) with an infusion of dobutamine≥5 μg kg(-1) min(-1) and decreased by 40% from baseline (COdown) infusing sodium nitroglycerine≥30 μg kg(-1) min(-1) plus esmolol 500 μg kg(-1) min(-1). Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07). Invasive hemodynamic data and VCap were recorded and compared before and after each step using a mixed random effects model. Compared to baseline, the normalized slope of phase III (SnIII) increased by 32% in PHT25 and by 22% in PHT40. SnIII decreased non-significantly by 4% with COdown. A combination of PHT and COdown associated with severe hypoxemia increased SnIII by 28% compared to baseline. The elimination of CO2 per breath decreased by 7% in PHT40 and by 12% in COdown but increased only slightly with COup. Dead space variables did not change significantly along the protocol. At constant ventilation and body metabolism, pulmonary artery hypertension and decreases in CO had the biggest effects on the SnIII of the volumetric capnogram and on the elimination of CO2.