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.

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.

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.

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.

Correlation of plasma coagulation tests and fibrinogenClauss with rotational thromboelastometry parameters and prediction of bleeding in dogs.

BACKGROUND: Correlation of plasma fibrinogen concentration (fibrinogenClauss ) with rotational thromboelastometry (ROTEM) parameters has not been investigated in dogs. OBJECTIVES: To determine the correlation between plasma coagulation tests and fibrinogenClauss with ROTEM parameters and to evaluate their ability to predict bleeding in dogs. ANIMALS: Ninety-seven dogs with concurrent determination of fibrinogenClauss and fibrin polymerization test (FIBTEM) analysis. METHODS: Signalment, pretreatment, clinical signs of bleeding, fibrinogenClauss , plasma coagulation test results, hematocrit, platelet count, FIBTEM, extrinsic (EXTEM) and intrinsic (INTEM) activated ROTEM assays were retrieved retrospectively. Correlations between fibrinogenClauss and FIBTEM maximum clot firmness (MCFFIBTEM ) and between prothrombin time (PT) or activated partial thromboplastin time (aPTT) and ROTEM parameters were determined. Dogs were further assigned to groups with or without clinical signs of bleeding. The prognostic significance of significantly different parameters to predict bleeding was evaluated. RESULTS: FibrinogenClauss showed strong correlation with MCFFIBTEM (r = 0.860, n = 97, P < .001). PT showed strong correlation with EXTEM clotting time (CTEXTEM ) (r = 0.839, n = 53, P < .001), and aPTT was strongly correlated with INTEM CT (CTINTEM ) (r = 0.664, n = 31, P < .001). Platelet count, PT/aPTT, EXTEM clot formation time (CFTEXTEM ), MCFEXTEM , EXTEM maximum clot elasticity (MCEEXTEM ), and CTINTEM were significantly different between groups. A CTINTEM >149 seconds was 100% sensitive to detect bleeding. CONCLUSIONS AND CLINICAL IMPORTANCE: The MCFFIBTEM can be used to evaluate the effect of fibrinogen on hemostasis as an alternative to determination of fibrinogenClauss . In addition, CTEXTEM and CTINTEM are strongly correlated with PT and aPTT, respectively.

Comparison of three continuous positive airway pressure (CPAP) interfaces in healthy Beagle dogs during medetomidine-propofol constant rate infusions.

OBJECTIVE: To compare the efficacy of three continuous positive airway pressure (CPAP) interfaces in dogs on gas exchange, lung volumes, amount of leak during CPAP and rebreathing in case of equipment failure or disconnection. STUDY DESIGN: Randomized, prospective, crossover, experimental trial. ANIMALS: Ten purpose-bred Beagle dogs. METHODS: Dogs were in dorsal recumbency during medetomidine-propofol constant rate infusions, breathing room air. Three interfaces were tested in each dog in a consecutive random order: custom-made mask (M), conical face mask (FM) and helmet (H). End-expiratory lung impedance (EELI) measured by electrical impedance tomography was assessed with no interface (baseline), with the interface only (No-CPAP for 3 minutes) and at 15 minutes of 7 cmH2O CPAP (CPAP-delivery). PaO2 was assessed at No-CPAP and CPAP-delivery, partial pressure of inspired carbon dioxide (PICO2; rebreathing assessment) at No-CPAP and the interface leak (ΔPleak) at CPAP-delivery. Mixed-effects linear regression models were used for statistical analysis (p<0.05). RESULTS: During CPAP-delivery, all interfaces increased EELI by 7% (p<0.001). Higher ΔPleak was observed with M and H (9 cmH2O) in comparison with FM (1 cmH2O) (p<0.001). At No-CPAP, less rebreathing occurred with M (0.5 kPa, 4 mmHg) than with FM (1.8 kPa, 14 mmHg) and with H (1.4 kPa, 11 mmHg), but also lower PaO2 was measured with M (9.3 kPa, 70 mmHg) than with H (11.9 kPa, 90 mmHg) and FM (10.8 kPa, 81 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: All three interfaces can be used to provide adequate CPAP in dogs. The leak during CPAP-delivery and the risk of rebreathing and hypoxaemia, when CPAP is not maintained, can be significant. Therefore, animals should always be supervised during administration of CPAP with any of the three interfaces. The performance of the custom-made M was not superior to the other interfaces.

Reference values for rotational thromboelastometry (ROTEM) in clinically healthy cats.

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 2.5-97.5th 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.

Clinical evaluation of intranasal medetomidine-ketamine and medetomidine-S(+)-ketamine for induction of anaesthesia in rabbits in two centres with two different administration techniques.

OBJECTIVE: The aim was to compare efficacy and side effects of induction with medetomidine-ketamine or medetomidine-S(+)-ketamine by intranasal (IN) instillation in rabbits and to evaluate both protocols during subsequent isoflurane anaesthesia. STUDY DESIGN: Prospective, blinded, randomized experimental study in two centres. ANIMALS: Eighty-three healthy New Zealand White rabbits undergoing tibial or ulnar osteotomy. METHODS: Medetomidine (0.2 mg kg-1) with 10 mg kg-1 ketamine (MK) or 5 mg kg-1 S(+)-ketamine (MS) was administered IN to each rabbit in a randomized fashion. In Centre 1 (n = 42) rabbits were held in sternal recumbency, and in Centre 2 (n = 41) in dorsal recumbency, during drug instillation. Adverse reactions were recorded. If a rabbit swallowed during endotracheal intubation, half of the initial IN dose was repeated and intubation was re-attempted after 5 minutes. Anaesthesia was maintained with isoflurane. Heart rate, blood pressure, endtidal carbon dioxide concentration and blood gases were recorded. Data were analysed using Student's t-test, Mann-Whitney test and Fisher's exact test. RESULTS: In all, 39 animals were assigned to the MK group and 44 to the MS group. Two rabbits in the MS group held in dorsal recumbency died after instillation of the drug. Eight (MK) and 11 rabbits (MS) were insufficiently anaesthetized and received a second IN dose. One rabbit in MK and three in MS required an isoflurane mask induction after the second IN dose. There were no significant differences between treatments for induction, intraoperative data, blood gas values and recovery data. CONCLUSION AND CLINICAL RELEVANCE: This study indicated that medetomidine-ketamine and medetomidine-S(+)-ketamine were effective shortly after IN delivery, but in dorsal recumbency IN administration of S(+)-ketamine led to two fatalities. Nasal haemorrhage was noted in both cases; however, the factors leading to death have not been fully elucidated.

Pharmacokinetics of ketamine and three metabolites in Beagle dogs under sevoflurane vs. medetomidine comedication assessed by enantioselective capillary electrophoresis.

Ketamine is often used for anesthesia in veterinary medicine. One possible comedication is the sedative α2-agonist medetomidine. Advantages of that combination are the compensation of side effects of the two drugs and the anesthetic-sparing effect of medetomidine. In vitro studies showed that medetomidine has an inhibitive effect on the formation of norketamine. Norketamine is the first metabolite of ketamine and is also active. It is followed by others like 6-hydroxynorketamine and 5,6-dehydronorketamine (DHNK). In an in vivo pharmacokinetic study Beagle dogs under sevoflurane anesthesia (mean end-tidal concentration 3.0±0.2%) or following medetomidine sedation (450µg/m2) received 4mg/kg racemic ketamine or 2mg/kg S-ketamine. Blood samples were collected between 0 and 900min after drug injection. 50µL aliquots of plasma were pretreated by liquid-liquid extraction prior to analysis of the reconstituted extracts with a robust enantioselective capillary electrophoresis assay using highly sulfated γ-cyclodextrin as chiral selector and electrokinetic sample injection of the analytes from the extract across a short buffer plug without chiral selector. Levels of S- and R-ketamine, S- and R-norketamine, (2S,6S)- and (2R,6R)-hydroxynorketamine and S- and R-DHNK were determined. Data were analyzed with compartmental pharmacokinetic models which included two compartments for the ketamine and norketamine enantiomers and a single compartment for the DHNK and 6-hydroxynorketamine stereoisomers. Medetomidine showed an effect on the formation and elimination of all metabolites. Stereoselectivities were detected for 6-hydroxynorketamine and DHNK, but not for ketamine and norketamine.

Evaluation of agreement and trending ability between transpulmonary thermodilution and calibrated pulse contour and pulse power cardiac output monitoring methods against pulmonary artery thermodilution in anesthetized dogs.

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.

Evaluation of the non-calibrated pulse contour cardiac output monitor FloTrac/Vigileo against thermodilution in standing horses.

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.