The influence of hypoxaemia, hypotension and hypercapnia (among other factors) on quality of recovery from general anaesthesia in horses.

OBJECTIVE: To investigate the effect of hypoxaemia, hypotension and hypercapnia, among others, on quality of recovery from general anaesthesia in horses. STUDY DESIGN: Retrospective, single-centre study. ANIMALS: A sample of 1226 horses that underwent general anaesthesia between June 2017 and June 2021. METHODS: Horses and ponies weighing > 200 kg, aged > 6 months, anaesthetized using a xylazine- or medetomidine-isoflurane balanced anaesthesia protocol and presenting a complete anaesthetic record were included. Data were extracted from the clinic record system and from the original anaesthesia records. Recoveries were divided into 'good' and 'bad' based on the available recovery scores. Influence of hypoxaemia [PaO2 < 60 mmHg (7.99 kPa)], hypotension (mean arterial pressure < 70 mmHg for at least 15 minutes) and hypercapnia [PaCO2 > 60 mmHg (7.99 kPa)], anaesthesia protocol, body weight, age, breed, sex, American Society of Anesthesiologists status, type of procedure, emergency or nonemergency, duration of anaesthesia, positioning, times spent in lateral and sternal recumbency during recovery, time until standing and nonassisted or assisted recovery on the assigned recovery score (good/bad) were investigated using generalized linear regression analysis (p < 0.05). RESULTS: Hypoxaemia and prolonged duration of anaesthesia were significantly associated with a bad recovery score. No other factors had a significant influence on recovery quality. CONCLUSION AND CLINICAL RELEVANCE: Hypoxaemia and prolonged anaesthesia duration have a negative effect on quality of anaesthetic recovery in horses. Clinically, this highlights the importance of keeping anaesthetic time as short as possible and to monitor oxygenation and treat hypoxaemia as soon as possible.

Effects of hypothermia and hypothermia combined with hypocapnia on cerebral tissue oxygenation in piglets.

BACKGROUND: Hypothermia and its combination with hypocapnia are frequently associated with anesthesia. AIMS: The goal was to investigate the effects of hypothermia and hypothermia combined with hypocapnia (hypothermia-hypocapnia) on cerebral tissue oxygenation in anesthetized piglets. METHODS: Twenty anesthetized piglets were randomly allocated to hypothermia (n = 10) or hypothermia-hypocapnia (n = 10). Cerebral monitoring comprised a tissue oxygen partial pressure (PtO2 ), a laser Doppler probe, and a near-infrared spectroscopy sensor, measuring regional oxygen saturation (rSO2 ). After baseline recordings, hypothermia (35.5-36.0°C) with or without hypocapnia (target PaCO2 : 28-30 mm Hg) was induced. Once treatment goals were achieved (Tr0), they were maintained for 30 minutes (Tr30). RESULTS: No changes in PtO2 but a significant increase in rSO2 (Tr0 (mean difference 8.9[95% CI for difference3.99 to 13.81], P < .001); Tr30 (10.8[6.20 to 15.40], P < .001)) were detected during hypothermia. With hypothermia-hypocapnia, a decrease in PtO2 (Tr0 (-3.2[-6.01 to -0.39], P = .021; Tr30 (-3.3[-5.8 to -0.80], P = .006)) and no significant changes in rSO2 occurred. Cerebral blood flow decreased significantly from baseline to Tr0 independently of treatment (-0.89[-0.18 to -0.002], P = .042), but this was more consistently observed with hypothermia-hypocapnia. CONCLUSIONS: The hypothermia-induced reduction in oxygen delivery was compensated by lowered metabolic demand. However, hypothermia was not able to compensate for an additional reduction in oxygen delivery caused by simultaneous hypocapnia. This resulted in a PtO2 drop, which was not reflected by a downshift in rSO2 .

Effects of moderate and severe hypocapnia on intracerebral perfusion and brain tissue oxygenation in piglets.

BACKGROUND: Hypocapnia is a common alteration during anesthesia in neonates. AIM: To investigate the effects of hypocapnia and hypocapnia combined with hypotension (HCT) on cerebral perfusion and tissue oxygenation in anesthetized piglets. METHOD: Thirty anesthetized piglets were randomly allocated to groups: moderate hypocapnia (mHC), severe hypocapnia (sHC), and HCT. Cerebral monitoring comprised a tissue oxygen partial pressure and a laser Doppler probe inserted into the brain tissue as well as a near-infrared spectroscopy (NIRS) sensor placed on the skin, measuring regional oxygen saturation. Hypocapnia was induced by hyperventilation (target PaCO2 mHC: 3.7-4; sHC: 3.1-3.3 kPa) and hypotension by blood withdrawal and nitroprusside infusion (mean blood pressure: 35-38 mm Hg). Data were analyzed at baseline, during (Tr20, Tr40, Tr60) and after (Post20, Post40, Post60) treatment. RESULTS: Compared to baseline, tissue oxygen partial pressure decreased significantly and equally during all treatments (mean [SD] at baseline: mHC 35.7 [32.45]; sHC: 28.1 [20.24]; HCT 25.4 [10.3] and at Tr60: mHC: 29.9 [27.36]; sHC: 22.2 [18.37]; HCT: 18.4 [9.5] mm Hg). Decreased laser Doppler flow was detected with all treatments at Tr20 (mHC: 0.9 [0.18]; sHC: 0.88 [0.15]; HCT: 0.97 [0.13] proportion from baseline). Independently of group, regional oxygen saturation varied only after reverting and not during treatment. Blood lactate, pH, HCO3- , and PaO2 increased during treatment with no differences between groups. CONCLUSION: This animal model revealed reduced cerebral blood flow and brain tissue oxygenation during hypocapnia without detectable changes in regional oxygen saturation as measured by NIRS. Changes occurred as early as during moderate hypocapnia.

Cardiovascular effects of two adenosine constant rate infusions in anaesthetized dogs.

OBJECTIVE: Adenosine induces vasodilatation. The aim of this study was to investigate cardiovascular effects of two adenosine constant rate infusion (CRI) doses in dogs. STUDY DESIGN: Experimental, longitudinal repeated measure design. ANIMALS: Ten healthy purpose-bred Beagle dogs. METHODS: Each dog was sedated with butorphanol. Anaesthesia was induced with propofol intravenously and maintained with sevoflurane (inspired oxygen fraction = 47-55%). Controlled mechanical ventilation was used to maintain normocapnia. Two doses of adenosine were administered as CRIs to each dog: 140 µg kg-1 minute-1 (A140) followed by 280 µg kg-1 minute-1 (A280). Pulse rate, invasive arterial pressure and stroke volume (by magnetic resonance phase contrast angiography) were measured at baseline, 3 minutes after starting adenosine and 3 and 10 minutes after discontinuing adenosine. Cardiac output, cardiac index and approximated systemic vascular resistances (approximate SVR) were calculated. Additionally, arterial blood gases, co-oximetry, electrolytes, glucose and lactate were measured and oxygen content and delivery calculated. One-way repeated measures analysis of variance (p < 0.05) was used for data analysis. RESULTS: A140 and A280 resulted in a significant decrease in arterial blood pressure [systolic (p = 0.008), mean (p = 0.003), and diastolic arterial pressure (p = 0.004)] and approximate SVR (p = 0.008) compared with baseline. No significant changes were detected for the other variables. All values returned to baseline within 3 minutes after adenosine discontinuation. CONCLUSIONS AND CLINICAL RELEVANCE: Adenosine CRI decreases arterial pressure by vasodilatation in healthy dogs. No additional effects were observed with the higher dose. The effects in compromised dogs remain to be investigated.

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.

Clinical comparison of dexmedetomidine and medetomidine for isoflurane balanced anaesthesia in horses.

OBJECTIVE: To compare the effects of two balanced anaesthetic protocols (isoflurane-dexmedetomidine versus medetomidine) on sedation, cardiopulmonary function and recovery in horses. STUDY DESIGN: Prospective, blinded, randomized clinical study. ANIMALS: Sixty healthy adult warm blood horses undergoing elective surgery. METHODS: Thirty horses each were sedated with dexmedetomidine 3.5 µg kg-1 (group DEX) or medetomidine 7 µg kg-1 (group MED) intravenously. After assessing and supplementing sedation if necessary, anaesthesia was induced with ketamine/diazepam and maintained with isoflurane in oxygen/air and dexmedetomidine 1.75 µg kg-1 hour-1 or medetomidine 3.5 µg kg-1 hour-1. Ringer's lactate (7-10 mL kg-1 hour-1) and dobutamine were administered to maintain normotension. Controlled mechanical ventilation maintained end-tidal expired carbon dioxide pressures at 40-50 mmHg (5.3-6.7 kPa). Heart rate, invasive arterial blood pressure, inspired and expired gas composition and arterial blood gases were measured. Dexmedetomidine 1 µg kg-1 or medetomidine 2 µg kg-1 was administered for timed and scored recovery phase. Data were analysed using two-way repeated-measures analysis of variance and chi-square test. Significance was considered when p≤0.05. RESULTS: In group DEX, significantly more horses (n=18) did not fulfil the sedation criteria prior to induction and received one or more supplemental doses, whereas in group MED only two horses needed one additional bolus. Median (range) total sedation doses were dexmedetomidine 4 (4-9) µg kg-1 or medetomidine 7 (7-9) µg kg-1. During general anaesthesia, cardiopulmonary parameters did not differ significantly between groups. Recovery scores in group DEX were significantly better than in group MED. CONCLUSIONS AND CLINICAL RELEVANCE: Horses administered dexmedetomidine required more than 50% of the medetomidine dose to reach equivalent sedation. During isoflurane anaesthesia, cardiopulmonary function was comparable between the two groups. Recovery scores following dexmedetomidine were better compared to medetomidine.

Effects of hypotension and/or hypocapnia during sevoflurane anesthesia on perfusion and metabolites in the developing brain of piglets-a blinded randomized study.

BACKGROUND: Hypotension (HT) and/or hypocapnia (HC) are frequent complications occurring during pediatric anesthesia and may cause cerebral injury in the developing brain. AIM: The aim of this study is to investigate the effects of HT and/or HC on perfusion and metabolism in the developing brain. METHODS: Twenty-eight piglets were randomly allocated to four groups: control (C), HT, HC, and hypotension and hyocapnia (HTC). Anesthesia was induced and maintained using sevoflurane. Fentanyl was added for instrumentation. Piglets were fully monitored and their lungs were artificially ventilated. Before treatment, conventional magnetic resonance imaging (MRI), dynamic susceptibility-contrast-enhanced T2*-weighted MRI (DSC-MRI), and single voxel proton MR spectroscopy ((1) H MRS) were performed. Hypotension (mean arterial blood pressure: 30 ± 3 mmHg) was induced by blood withdrawal and nitroprusside infusion, and hyperventilation was used to induce HC (PaCO2 : 2.7-3.3 kPa). (1) H MRS and DSC-MRI were repeated immediately once treatment goals were achieved and 120 min later. Radiologists were blinded to the groups. DSCI-MRI and (1) H MRS analyses were performed in the thalamus, occipital and parietal lobe, hippocampus, and watershed areas. RESULTS: In comparison to C, mean time to peak (TTP) increased with HTC in all brain areas as assessed with DSC-MRI (n = 26). Using (1) H MRS, a significant decrease in N-acetyl aspartate, choline, and myoinositol, as well as an increase in glutamine-glutamate complex (Glx) were detected independent of group. Compared to C, changes were more pronounced for Glx (due to an increase in glutamate) and myoinositol with HTC, for N-acetyl aspartate with HT, and for Glx with HC. No lactate signal was present. CONCLUSIONS: The combination of HT and HC during sevoflurane anesthesia resulted in alteration of cerebral perfusion with signs of neuronal dysfunction and early neuronal ischemia. HT and HC alone also resulted in signs of metabolic disturbances despite the absence of detectable cerebral perfusion alterations.

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.

Cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane and low-dose S-ketamine or medetomidine infusions.

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 PaO2 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.

Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses.

OBJECTIVE: To compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses. STUDY DESIGN: Prospective 'blinded' controlled trial using block randomization. ANIMALS: Forty healthy Freiberger stallions. METHODS: The horses received either intravenous (IV) romifidine (loading dose: 80 µg kg(-1) ; infusion: 30 µg kg(-1)  hour(-1) ) (treatment R, n = 20) or romifidine combined with butorphanol (romifidine loading: 80 µg kg(-1) ; infusion: 29 µg kg(-1)  hour(-1) , and butorphanol loading: 18 µg kg(-1) ; infusion: 25 µg kg(-1)  hour(-1) ) (treatment RB, n = 20). Twenty-one horses underwent dentistry and ophthalmic procedures, while 19 horses underwent only ophthalmologic procedure and buccal examination. During the procedure, physiologic parameters and occurrence of head/muzzle shaking or twitching and forward movement were recorded. Whenever sedation was insufficient, additional romifidine (20 µg kg(-1) ) was administered IV. Recovery time was evaluated by assessing head height above ground. At the end of the procedure, overall quality of sedation for the procedure was scored by the dentist and anaesthetist using a visual analogue scale. Statistical analyses used two-way anova or linear mixed models as relevant. RESULTS: Sedation quality scores as assessed by the anaesthetist were R: median 7.55, range: 4.9-9.0 cm, RB: 8.8, 4.7-10.0 cm, and by the dentist R: 6.6, 3.0-8.2 cm, RB: 7.9, 6.6-8.8 cm. Horses receiving RB showed clinically more effective sedation as demonstrated by fewer poor scores and a tendency to reduced additional drug requirements. More horses showed forward movement and head shaking in treatment RB than treatment R. Three horses (two RB, one R) had symptoms of colic following sedation. CONCLUSIONS AND CLINICAL RELEVANCE: The described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous.

Intravenous versus intramuscular epinephrine administration during cardiopulmonary resuscitation - a pilot study in piglets.

BACKGROUND: Early epinephrine administration in cardiac arrest seems to be advantageous to achieve return of spontaneous circulation (ROSC). Because intravenous (i.v.) or intraosseous access is not always immediately available, this study compares efficacy of early intramuscular (i.m.) epinephrine administration with early and delayed i.v. epinephrine injection in an animal cardiac arrest model. METHODS: Piglets anesthetized with sevoflurane were intoxicated by an i.v. ropivacaine infusion until circulatory arrest. After 1 min basic life support (chest compression and ventilation), epinephrine i.v. (10 µg·kg(-1), group IV) or epinephrine i.m. (100 µg·kg(-1), group IM) or normal saline (group NS) was applied. Further doses of epinephrine were given in group IV every 4 min and in group IM after 10 min if required. Twenty-one minutes after circulatory arrest, i.v. epinephrine - as necessary - was given to all animals. Thus, group NS represents late epinephrine administration. Outcomes were survival and time to ROSC. RESULTS: Twenty-four pigs aged 19.5 (median, interquartile range 16-22) days, weighing 5.4 (5.0-5.7) kg were investigated. Total amount of ropivacaine administered was 8.9 (8.1-10.1) mg·kg(-1). Cardiac rhythm before starting CPR was pulseless electric activity and asystole in 15 and 9 pigs, respectively. Eight, seven, and four pigs survived in group IV, IM, and NS. Focusing on surviving animals, time to ROSC was 2, 4 and 19.5 min in group IV, IM, and NS. CONCLUSIONS: Early i.m. epinephrine provided similar survival compared with early i.v. epinephrine and was superior to delayed epinephrine administration in resuscitation of ropivacaine-induced cardiac arrest in piglets.

Electrocardiographic and blood pressure alterations caused by intravenous injection of ropivacaine - a study in piglets.

OBJECTIVES: Objective signs to detect inadvertent intravascular injection of local anesthetics are essential in the anesthetized pediatric patient. For early detection of intravenous bupivacaine administration, it was shown that an epinephrine containing test dose reliably provoked T-wave alterations, changes in heart rate (HR) and blood pressure, whereas intravenous injection of plain bupivacaine could not be detected until high doses were applied. This study investigates electrocardiographic and hemodynamic alterations caused by intravenous ropivacaine. METHODS: Twenty-four piglets, anesthetized with sevoflurane, were randomized into two groups: Group R received as test dose plain ropivacaine 0.2% and group RE, ropivacaine 0.2% + epinephrine 5 µg·ml(-1) . Under stable conditions, 0.2 ml kg(-1) of the test solution was intravenously injected. Twenty minutes later, 0.4 ml kg(-1) was applied. A positive effect was defined as HR increase ≥ 10 bpm, increase in mean arterial pressure (MAP) ≥ 15 mmHg, T-wave increase ≥ 25% baseline. In another setting ropivacaine was intravenously infused until cardiac arrest. RESULTS: After injection of 0.2 or 0.4 ml kg(-1) test solution, a positive increase in HR and MAP was found in 0% of group R and in 100% of group RE. An increase in T-wave ≥ 25% was found in 42% of group R and in 100% of group RE. During intoxication, T-elevation was seen in 83%. CONCLUSIONS: An epinephrine containing test dose ropivacaine reliably provoked T-wave elevations and increases in HR and MAP. A small dose plain ropivacaine caused T-elevations in a remarkable percentage, whereas higher, quite toxic doses provoked T-elevations in most of the pigs.

The effects of a loading dose followed by constant rate infusion of xylazine compared with romifidine on sedation, ataxia and response to stimuli in horses.

OBJECTIVE: To compare xylazine and romifidine constant rate infusion (CRI) protocols regarding degree of sedation, and effects on postural instability (PI), ataxia during motion (A) and reaction to different stimuli. STUDY DESIGN: Blinded randomized experimental cross-over study. ANIMALS: Ten adult horses. METHODS: Degree of sedation was assessed by head height above ground (HHAG). Effects on PI, A and reaction to visual, tactile and acoustic stimulation were assessed by numerical rating scale (NRS) and by visual analogue scale (VAS). After baseline measurements, horses were sedated by intravenous loading doses of xylazine (1 mg kg(-1) ) or romifidine (80 µg kg(-1) ) administered over 3 minutes, immediately followed by a CRI of xylazine (0.69 mg kg(-1 ) hour(-1) ) or romifidine (30 µg kg(-1 ) hour(-1) ) which was administered for 120 minutes. Degree of sedation, PI, A and reaction to the different stimuli were measured at different time points before, during and for one hour after discontinuing drug administration. Data were analysed using two-way repeated measures anova, a Generalized Linear Model and a Wilcoxon Signed Rank Test (p < 0.05). RESULTS: Significant changes over time were seen for all variables. With xylazine HHAG was significantly lower 10 minutes after the loading dose, and higher at 150 and 180 minutes (i.e. after CRI cessation) compared to romifidine. Reaction to acoustic stimulation was significantly more pronounced with xylazine. Reaction to visual stimulation was greater with xylazine at 145 and 175 minutes. PI was consistently but not significantly greater with xylazine during the first 30 minutes. Reaction to touch and A did not differ between treatments. Compared to romifidine, horses were more responsive to metallic noise with xylazine. CONCLUSIONS: Time to maximal sedation and to recovery were longer with romifidine than with xylazine. CLINICAL RELEVANCE: With romifidine sufficient time should be allowed for complete sedation before manipulation.

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.

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.

Delivery of non-viral naked DNA vectors to liver in small weaned pigs by hydrodynamic retrograde intrabiliary injection.

Hepatic gene therapy by delivering non-integrating therapeutic vectors in newborns remains challenging due to the risk of dilution and loss of efficacy in the growing liver. Previously we reported on hepatocyte transfection in piglets by intraportal injection of naked DNA vectors. Here, we established delivery of naked DNA vectors to target periportal hepatocytes in weaned pigs by hydrodynamic retrograde intrabiliary injection (HRII). The surgical procedure involved laparotomy and transient isolation of the liver. For vector delivery, a catheter was placed within the common bile duct by enterotomy. Under optimal conditions, no histological abnormalities were observed in liver tissue upon pressurized injections. The transfection of hepatocytes in all tested liver samples was observed with vectors expressing luciferase from a liver-specific promoter. However, vector copy number and luciferase expression were low compared to hydrodynamic intraportal injection. A 10-fold higher number of vector genomes and luciferase expression was observed in pigs using a non-integrating naked DNA vector with the potential for replication. In summary, the HRII application was less efficient (i.e., lower luciferase activity and vector copy numbers) than the intraportal delivery method but was significantly less distressful for the piglets and has the potential for injection (or re-injection) of vector DNA by endoscopic retrograde cholangiopancreatography.

A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics.

OBJECTIVE: To test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine-isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics. STUDY DESIGN: Prospective blinded randomised clinical trial. ANIMALS: 61 horses undergoing elective surgery. METHODS: Horses were sedated with intravenous (i.v.) medetomidine (7 µg kg(-1)); anaesthesia was induced with i.v. ketamine (2.2 mg kg(-1)) and diazepam (0.02 mg kg(-1)) and maintained with isoflurane and a CRI of medetomidine (3.5 µg kg(-1) hour(-1)). Group MB (n = 31) received butorphanol CRI (25 µg kg(-1) i.v. bolus then 25 µg kg(-1) hour(-1)); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO2 in the normal range. Horses received lactated Ringer's solution 5 mL kg(-1) hour(-1), dobutamine <1.25 µg kg(-1) minute(-1) and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann-Whitney Rank Sum test (p < 0.05). RESULTS: There was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute(-1)), pH, PaO2 (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes). CONCLUSION AND CLINICAL RELEVANCE: Butorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine-isoflurane and has no influence on cardiopulmonary function or recovery.

Comparison of Recovery Quality Following Medetomidine versus Xylazine Balanced Isoflurane Anaesthesia in Horses: A Retrospective Analysis.

Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was used: sedation with 7 µg·kg-1 medetomidine or 1.1 mg·kg-1 xylazine, anaesthesia induction with ketamine/diazepam, maintenance with isoflurane and 3.5 µg·kg-1·h-1 medetomidine or 0.7 mg·kg-1·h-1 xylazine, and sedation after anaesthesia with 2 µg·kg-1 medetomidine or 0.3 mg·kg-1 xylazine. Recovery was timed and, using video recordings, numerically scored by two blinded observers. Influence of demographics, procedure, peri-anaesthetic drugs, and intraoperative complications (hypotension, hypoxemia, and tachycardia) on recovery were analysed using regression analysis (p < 0.05). A total of 470 recoveries (medetomidine 279, xylazine 191) were finally included. Following medetomidine, recoveries were significantly longer (median (interquartile range): 57 (43-71) min) than xylazine (43 (32-59) min) (p < 0.001). However, the number of attempts to stand was similar (medetomidine and xylazine: 2 (1-3)). Poorer scores were seen with increased pre-anaesthetic dose of xylazine, intraoperative tetrastarch, or salbutamol. However, use of medetomidine or xylazine did not influence recovery score, concluding that, following medetomidine-isoflurane PIVA, recovery is longer, but of similar quality compared to xylazine.