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

IntroductionIn 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.MethodsIn 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.ResultsTwelve 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.DiscussionMRS 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

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

Resting state networks of the canine brain under sevoflurane anaesthesia

Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs’ brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases

The influence of anaesthetic drugs on the laryngeal motion in dogs: a systematic review

Anaesthetic drugs are commonly used during the evaluation of laryngeal function in dogs. The aim of this review was to systematically analyse the literature describing the effects of anaesthetic drugs and doxapram on laryngeal motion in dogs and to determine which drug regime provides the best conditions for laryngeal examination. PubMed, Google Scholar, and EMBASE databases were used for the literature search up to November 2019. Relevant search terms included laryngeal motion, anaesthetic drugs and dogs. Studies were scored based on their level of evidence (LoE), according to the Oxford Centre for Evidence-based Medicine, and the quality was assessed using the risk-of-bias tool and SIGN-checklist. In healthy dogs, premedication before laryngeal examination provided better examination conditions and maintained overall adequate laryngeal motion in 83% of the studies. No difference in laryngeal motion between induction drugs was found in 73% of the studies but the effects in dogs with laryngeal paralysis remain largely unknown. Doxapram increased laryngeal motion in healthy dogs without serious side effects, but intubation was necessary for some dogs with laryngeal paralysis. Methodological characteristics varied considerably between studies, including the technique and timing of evaluation, number of assessors, study design, drug dose, combinations, route and speed of administration

Trending ability and limitations of transpulmonary thermodilution and pulse contour cardiac output measurement in cats as a model for pediatric patients

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

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

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

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

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

Pulmonary hypertension

OBJECTIVES: The purposes of this study were to evaluate if (1) Angiostrongylus vasorum-infected dogs recruit pulmonary arteriovenous (AV) shunts attenuating the development of pulmonary hypertension (PH), detectable using saline contrast echocardiography, (2) anthelmintic therapy causes an acute increase in pulmonary arterial pressure (PAP), (3) Tissue Doppler Imaging (TDI) allows detection of mild changes in right ventricular function secondary to pulmonary (vascular) disease. ANIMALS: 6 healthy Beagle dogs, each infected with 200 A. vasorum larvae. METHODS: Conventional, TDI and contrast echocardiography, invasive PAP measurements before (T0), 7-12 weeks post infection (wpi, T1), and 1-5 days post therapy (dpt, T2). RESULTS: All dogs had patent infections 7-8 wpi and respiratory signs 6-9 wpi. PAP was mildly but significantly increased at T2. Saline contrast echo was positive in 3/6 dogs at T1 and 4/6 dogs at T2. Pulmonary transit time did not change. Of all numeric echocardiographic parameters, only a non-significant decrease in the E' wave and inversion of E'/A' ratio in 3 dogs at T2 could be observed. Two of these had mild PH and negative saline contrast echocardiography. CONCLUSION: A. vasorum infection causes only a mild increase in PAP following inoculation and anthelmintic therapy. The absence of important PH may in part be explained by the recruitment of AV shunts in the presence of vascular obstructive disease. TDI echocardiographic parameters may be more sensitive to detect mild changes in RV function than conventional parameters