Sedative and cardiovascular effects of intranasal or intramuscular dexmedetomidine in healthy dogs.

OBJECTIVE: To compare the clinical effects and sedation scores following either intranasal (IN) or intramuscular (IM) administration of dexmedetomidine in dogs. STUDY DESIGN: Prospective, blinded, randomized, clinical study. ANIMALS: A total of 20 client-owned dogs scheduled for noninvasive diagnostic procedures. METHODS: Dogs were allocated to be administered dexmedetomidine 0.02 mg kg-1 IN (IN group) or IM (IM group). Sedation was scored before and at 5 minute intervals (for 45 minutes) after drug administration using a composite simple descriptive sedation scale giving a score of 0 (not sedated) to 13 (well sedated). Respiratory frequency (fR), heart rate, haemoglobin oxygen saturation (SpO2) and noninvasive arterial blood pressure were recorded every 5 minutes for 45 minutes. Normally distributed data were analyzed using two-way ANOVA and post hoc Sidak's multiple comparison test. Non-normally distributed data were compared using the Scheier Ray Hare test and post hoc Mann-Whitney U test. Statistical significance was set at p<0.05. RESULTS: Weight, age and sex were not different between groups. Dexmedetomidine onset of action after IN administration was not shorter compared to IM administration (6.3±3.3 versus 9.4±4.6 minutes, p=0.120). Sedation score in the IN group was higher [10 (0-11)] compared to the IM group [6 (0-8)] (p<0.001). At time of peak sedation, heart rate decreased 56% from baseline values in the IM group, and 18% in the IN group. No significant differences in SpO2 and fR were found between the two groups at any time point. No undesirable effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal dexmedetomidine 0.02 mg kg-1 produced effective sedation with less bradycardia and more profound sedation compared to IM administration in healthy dogs and may be considered as an alternative route for dexmedetomidine administration in dogs.

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.

Effects on cardiopulmonary function and oxygen delivery of doses of romifidine and xylazine followed by constant rate infusions in standing horses.

The objective of this study was to compare the cardiopulmonary effects of a xylazine or romifidine loading-dose, followed by a constant rate infusion (CRI) of the same α(2)-agonist. Nine research horses were treated in a randomized, blinded, crossover design with xylazine or romifidine. After instrumentation, a loading dose of intravenous xylazine (1mg/kg) or romifidine (80µg/kg) was administered, immediately followed by a CRI of xylazine (0.69mg/kg/h) or romifidine (30µg/kg/h) for a duration of 2h. Cardiopulmonary variables were recorded before bolus administration, during CRI, and for 1h after discontinuing drug administration. A significant decrease in haemoglobin concentration (tHb), arterial oxygen content (CaO(2)), oxygen delivery (D˙O(2)), mixed venous partial pressure of oxygen, heart rate, and cardiac output (Q˙t) followed the loading dose with both treatments. Carotid arterial blood pressure (ABP), systemic vascular resistance, and right atrial pressure (RAP) increased significantly. The increased ABP was followed by a significant decrease compared to baseline. Mean pulmonary arterial pressure increased significantly with romifidine only. No significant changes in stroke volume, arterial partial pressure of oxygen, and oxygen consumption were observed. Changes in Q˙t and RAP were more pronounced with romifidine. During CRI, tHb, and CaO(2) were significantly higher with romifidine, whereas D˙O(2) did not differ between treatments. Overall, cardiopulmonary effects were more pronounced and lasted longer with romifidine compared to xylazine. However, during CRI, there was no difference in D˙O(2) between drugs. With both α(2)-agonists, cardiovascular effects were most pronounced after loading dose administration and tended to stabilize during CRI.

A minimally-invasive closed chest myocardial occlusion-reperfusion model in rhesus monkeys (Macaca mulatta): monitoring by contrast-enhanced ultrasound imaging.

Myocardial infarction is frequently developed in canine and porcine models but exceptionally in non-human primates. The aim of this study was to develop a minimally invasive myocardial ischemic/reperfusion model in the monkey intended to be combined with imaging techniques, in particular myocardial contrast echocardiography (MCE). A balloon-tipped catheter was advanced via the femoral artery into the left anterior descending artery (LAD) under fluoroscopic guidance in ten anaesthetized male rhesus monkeys (Macaca mulatta). The balloon was inflated to completely occlude the vessel. Coronary angiography (CA) was performed to control the reality of the LAD occlusion/reperfusion. The ischemia period was followed by 3-6 h of reperfusion. Myocardial perfusion was evaluated during ischemia and at reperfusion by MCE using a novel ultrasound contrast agent (BR38). Occlusion was successfully induced during 18-50 min in nine out of the ten evaluated monkeys. ST segment elevation indicated myocardial ischemia. MCE showed complete transmural arrest of myocardial blood flow during the ischemia period and no persistent microvascular perfusion defects during reperfusion. A minimally invasive closed-chest model was successfully developed for creating myocardial ischemia in the rhesus monkey (Macaca mulatta). This technique could have an important role in mimicking acute coronary syndrome under physiologically and ethically-acceptable conditions. MCE provides non-invasively information on myocardial perfusion status, information not available from CA.

Development of a romifidine constant rate infusion with or without butorphanol for standing sedation of horses.

OBJECTIVE: To determine constant rate infusion (CRI) protocols for romifidine (R) and romifidine combined with butorphanol (RB) resulting in constant sedation and romifidine plasma concentrations. STUDY DESIGN: Blinded randomized crossover study. ANIMALS: Ten adult research horses. METHODS: Part I: After determining normal height of head above ground (HHAG = 100%), loading doses of romifidine (80 µg kg(-1)) with butorphanol (RB: 18 µg kg(-1)) or saline (R) were given intravenously (IV). Immediately afterwards, a butorphanol (RB: 25 µg kg(-1) hour(-1)) or saline (R) CRI was administered for 2 hours. The HHAG was used as marker of sedation depth. Sedation was maintained for 2 hours by additional romifidine (20 µg kg(-1) ) whenever HHAG > 50%. The dose rate of romifidine (µg kg(-1) hour(-1)) required to maintain sedation was calculated for both treatments. Part II: After loading doses, the romifidine CRIs derived from part I were administered in parallel to butorphanol (RB) or saline (R). Sedation and ataxia were evaluated periodically. Romifidine plasma concentrations were measured by HPLC-MS-MS at 0, 5, 10, 15, 30, 45, 60, 90, 105, and 120 minutes. Data were analyzed using paired t-test, Fisher's exact test, Wilcoxon signed rank test, and two-way anova for repeated measures (p < 0.05). RESULTS: There was no significant difference in romifidine requirements (R: 30; RB: 29 µg kg(-1) hour(-1)). CRI protocols leading to constant sedation were developed. Time to first additional romifidine bolus was significantly longer in RB (mean ± SD, R: 38.5 ± 13.6; RB: 50.5 ± 11.7 minutes). Constant plasma concentrations of romifidine were achieved during the second hour of CRI. Ataxia was greater when butorphanol was added. CONCLUSION: Romifidine bolus, followed by CRI, provided constant sedation assessed by HHAG. Butorphanol was ineffective in reducing romifidine requirements in unstimulated horses, but prolonged the sedation caused by the initial romifidine bolus. CLINICAL RELEVANCE: Both protocols need to be tested under clinical conditions.

Development of a xylazine constant rate infusion with or without butorphanol for standing sedation of horses.

OBJECTIVE: To elaborate constant rate infusion (CRI) protocols for xylazine (X) and xylazine/butorphanol (XB) which will result in constant sedation and steady xylazine plasma concentrations. STUDY DESIGN: Blinded randomized experimental study. ANIMALS: Ten adult research horses. METHODS: Part I: After normal height of head above ground (HHAG = 100%) was determined, a loading dose of xylazine (1 mg kg(-1) ) with butorphanol (XB: 18 µg kg(-1) ) or saline (X: equal volume) was given slowly intravenously (IV). Immediately afterwards, a CRI of butorphanol (XB: 25 µg kg(-1) hour(-1)) or saline (X) was administered for 2 hours. The HHAG was used as a marker of depth of sedation. Sedation was maintained for 2 hours by additional boluses of xylazine (0.3 mg kg(-1)) whenever HHAG >50%. The dose of xylazine (mg kg(-1) hour(-1)) required to maintain sedation was calculated for both groups. Part II: After the initial loading dose, the calculated xylazine infusion rates were administered in parallel to butorphanol (XB) or saline (X) and sedation evaluated. Xylazine plasma concentrations were measured by HPLC-MS-MS at time points 0, 5, 30, 45, 60, 90, and 120 minutes. Data were analyzed using paired t-test, Wilcoxon signed rank test and a 2-way anova for repeated measures (p < 0.05). RESULTS: There was no significant difference in xylazine requirements (X: 0.69, XB: 0.65 mg kg(-1) hour(-1)) between groups. With treatment X, a CRI leading to prolonged sedation was developed. With XB, five horses (part I: two, part II: three) fell down and during part II four horses appeared insufficiently sedated. Xylazine plasma concentrations were constant after 45 minutes in both groups. CONCLUSION: Xylazine bolus, followed by CRI, provided constant sedation. Additional butorphanol was ineffective in reducing xylazine requirements and increased ataxia and apparent early recovery from sedation in unstimulated horses. CLINICAL RELEVANCE: Data were obtained on unstimulated healthy horses and extrapolation to clinical conditions requires caution.

A study of the correlation between objective and subjective indices of recovery quality after inhalation anaesthesia in equids.

OBJECTIVE: To examine the association between objective and subjective descriptors used for assessing recovery quality in horses after anaesthesia. STUDY DESIGN: Prospective clinical study. ANIMALS: Two hundred and seventy-six equids (110 mares, 85 entire males and 81 geldings), ASA 1-5, weighing 50-850 kg and aged 1 month - 25 years. METHODS: Recoveries after general anaesthesia were assisted with head and tail ropes by two anaesthetists. One scored dichotomous objective descriptors (DOD) of recovery. Two dichotomous objective scales (DOS) were then generated from those descriptors. The same individual also scored overall recovery quality using a visual analogue scale (VAS). The second anaesthetist scored recovery (good or bad) using a dichotomous subjective scale (DSS). Each DOD, the DSS and VAS were compared with each other using Pearson's chi-square test. DOSs were compared to the DSS using Wilcoxon's test and to the VAS using a Spearman's correlation test. RESULTS: Most DODs were associated (p < 0.05) with DSS and VAS. The DSS was not associated with resting/not resting in sternal recumbency (p = 0.535) nor with the time spent in sternal recumbency (p = 0.09). VAS and DSS scores were strongly associated (p < 0.0001). The two DOSs were in agreement with DSS (p < 0.0001) and negatively correlated to VAS (r(1)(2) = 0.38, r(2)(2) = 0.34, respectively, p-value <0.0001). CONCLUSION: Objective descriptors were linked closely with the subjective evaluations of recovery quality except for the presence or absence of a sternal recumbency phase and its duration. CLINICAL RELEVANCE: These components may not be essential in recovery scoring systems. The DOS were in agreement with DSS and VAS and could be a useful tool for further studies on recoveries.

Castration of horses under total intravenous anaesthesia: analgesic effects of lidocaine.

OBJECTIVE: To evaluate the effects of local anaesthesia with lidocaine for castration of horses under intravenous anaesthesia. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Fifteen equidae, scheduled to undergo castration under total intravenous anaesthesia, were randomly distributed in two groups. One group received lidocaine injections (group L: two ponies, four horses, two donkeys) and the other received saline (group S: two ponies, three horses, two donkeys). METHODS: Behaviour, heart rate (HR) and respiratory rate (f(R)) were evaluated prior to anaesthesia. Body mass was measured using an electronic scale and testicular volumes were estimated. The animals were anaesthetized with acepromazine intramuscularly and romifidine intravenously followed 10 minutes later by ketamine. Following romifidine administration lidocaine or saline was administered subcutaneously along the incision line and by intratesticular and intrafunicular injection. Based on clinical observations (movement, f(R), and cranial nerve reflexes) incremental intravenous doses of ketamine and romifidine were administered. HR, f(R), oscillometric mean arterial blood pressure (MAP), duration of surgery, movement and additional doses were recorded. Surgical conditions were assessed using a visual analogue scale (VAS) and a simple descriptive scale (SDS). Recovery was assessed by two assistants, unaware of treatment, acting separately using a VAS and a SDS. Group means were compared using Mann-Whitney and Wilcoxon tests and the Kruskal-Wallis signed rank test for matched pairs used to compare groups at different points (p < 0.05). RESULTS: The number (median, range) of incremental doses (4 [1-5] compared to 1.5 [1-4]) and movements (1 [1-5] compared to 0 [0-1]) were higher (p = 0.01 for both) in the control group than in the lidocaine group. Groups were similar for other recorded variables. CONCLUSIONS AND CLINICAL RELEVANCE: These results show the effectiveness of lidocaine used as a local anaesthetic adjunct to intravenous anaesthesia in horses undergoing castration.