Comparison of inhaled salbutamol and salmeterol for the treatment of arterial hypoxaemia in anaesthetized horses: a randomized clinical trial.

OBJECTIVE: To compare the efficacy of inhaled salbutamol with salmeterol for the treatment of arterial hypoxaemia in anaesthetized horses. STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: A total of 108 client-owned horses (American Society of Anesthesiologists status I-V) anaesthetized for elective and emergency procedures. METHODS: Horses were premedicated with acepromazine [intramuscularly 0.1 mg kg-1 or intravenously (IV) 0.05 mg kg-1] and xylazine (0.6 mg kg-1 IV). Midazolam (0.06 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV) were combined to induce anaesthesia, and isoflurane in oxygen/air mixture (inspired oxygen fraction 0.7) was used for maintenance of anaesthesia. Mechanical ventilation was initiated without delay using the following ventilator settings: tidal volume 10 mL kg-1, respiratory rate 8 breaths minute-1, inspiratory-to-expiratory time ratio 1:2, no positive end-expiratory pressure. If arterial blood gas analysis revealed PaO2 < 100 mmHg (13.3 kPa), the administration of either inhaled salbutamol (2 µg kg-1) or salmeterol (0.5 µg kg-1) was randomly assigned Blood gas analysis was repeated 15 and 30 minutes after treatment. The intervention was considered successful when PaO2 after treatment ≥ 1.2 × PaO2 before treatment (i.e. ≥20% increase). PaO2 at 15 and 30 minutes was compared between groups using Mann-Whitney U test; p < 0.05 was considered significant. RESULTS: Of the 108 horses, 60 were administered salbutamol, 65% and 60% responded successfully at 15 and 30 minutes, increasing their initial PaO2 by 38% and 44%, respectively. The other 48 horses were administered salmeterol, 35% responded successfully at 15 and 30 minutes, increasing their initial PaO2 by 3% and 4%, respectively. PaO2 was significantly higher after salbutamol than after salmeterol at 15 and 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Using the described protocol, inhaled salbutamol was more effective than salmeterol in improving PaO2 in anaesthetized horses with value < 100 mmHg (13.3 kPa).

Retrospective study of the changes in dynamic compliance and ventilation/perfusion mismatch following salbutamol inhalation in hypoxaemic mechanically ventilated anaesthetized horses.

OBJECTIVE: To study the changes in dynamic compliance (Cdyn), ventilation/perfusion (V˙/ Q˙) mismatch and haemodynamic variables in hypoxaemic anaesthetized horses whose PaO2 increased following salbutamol inhalation. STUDY DESIGN: Retrospective, clinical, cohort study. ANIMALS: A group of 73 client-owned horses treated with salbutamol when PaO2 <100 mmHg (13.3 kPa) during anaesthesia. METHODS: Horses were divided into two groups: responders (R), where PaO2 after salbutamol ≥1.2 PaO2 before treatment (i.e. ≥20% increase), and non-responders (NR), where PaO2 after salbutamol <1.2 PaO2 before treatment. Demographic data and intraoperative variables before treatment were compared between R and NR. Cdyn, arterial to end-tidal carbon dioxide difference [P(a-E´)CO2], estimated ratio of dead space to tidal volume (est.VD/VT), estimated shunt fraction (F-shunt), heart rate, systolic, mean and diastolic arterial pressure and dobutamine requirements were compared before and after treatment within R and NR. For each variable, the difference (Δ) between values pre- and posttreatment was calculated and compared between groups R and NR. Numerical data were compared using univariate or bivariate analysis and categorical data were compared using chi-square test; p < 0.05. RESULTS: Of the 73 horses 50 were classified as R while 23 horses were classified as NR. There was no statistical difference between R and NR for demographic data or initial intraoperative variables except for body weight [R: 531 (170-715) kg, NR: 540 (420-914) kg]. While salbutamol did not alter Cdyn in either group, it significantly decreased P(a-E´)CO2, est.VD/VT and F-shunt in R only. ΔP(a-E´)CO2, Δest.VD/VT and ΔF-shunt were significantly greater in R (-17.8%, -19.0% and -24.1%, respectively) than in NR (11.5%, 6.6% and -0.3%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: In hypoxaemic anaesthetized horses responding to inhaled salbutamol by a ≥1.2 increase in PaO2 no change in Cdyn was detected, but indicators of V˙/ Q˙ mismatch improved.

Perioperative analgesic efficacy of lumbar erector spinae plane block in dogs undergoing hemilaminectomy: a randomized blinded clinical trial.

OBJECTIVE: To evaluate the perioperative analgesic effect of the unilateral lumbar erector spinae plane block (ESPBL) in dogs undergoing hemilaminectomy. STUDY DESIGN: Randomized, blinded clinical study. ANIMALS: A total of 30 client-owned dogs undergoing thoracolumbar or lumbar hemilaminectomy for intervertebral disc extrusion (IVDE). METHODS: Dogs were randomly assigned to receive a unilateral ESPBL, performed either with 0.4 mL kg-1 ropivacaine 0.5% [group ROPI (n = 15)] or with saline solution [CNT group (n = 15)]. Dogs were premedicated intravenously (IV) with acepromazine 5 µg kg-1 and methadone 0.2 mg kg-1, general anaesthesia was induced by administering IV midazolam 0.2 mg kg-1 and propofol to effect and maintained with isoflurane. Fentanyl was administered as rescue analgesia. Bradycardia [heart rate (HR) < 60 beats minute-1] with hypotension was treated with atropine IV. The Short-Form of the Glasgow Composite Pain Scale was used pre- and postoperatively at 1, 2, 4, 8, 12, 16, 20 and 24 hours after extubation, and methadone 0.2 mg kg-1 was administered IV when pain score was ≥ 5/20. HR and end-tidal concentration of isoflurane (Fe'Iso) were compared between groups with anova combined with a Dunnet's post hoc test. Time to the first rescue methadone and total dose of fentanyl (FENtot, µg kg-1 hour-1) and methadone (METtot, mg kg-1) in the first 24 postoperative hours were compared using unpaired Student's t test. Postoperative pain scores were compared with the Mann-Whitney test and atropine administration with a Fisher's exact test; p < 0.05. RESULTS: HR, Fe'Iso, FENtot, METtot and atropine administration were significantly lower in group ROPI compared to CNT. Postoperative analgesic effect was significantly longer, and pain scores were significantly lower in group ROPI for all time points. CONCLUSIONS AND CLINICAL RELEVANCE: Unilateral ESPBL with ropivacaine reduced perioperative opioid consumption and the occurrence of bradycardia in dogs undergoing hemilaminectomy.

Comparison of single-breath continuous positive airway pressure manoeuvre with inhaled salbutamol to improve oxygenation in horses anaesthetized for laparotomy.

OBJECTIVE: To compare the efficacy of single-breath continuous positive airway pressure manoeuvre (CPAP-M) with inhaled salbutamol, and a combination of both. STUDY DESIGN: Randomized, clinical study. ANIMALS: A total of 62 client-owned horses (American Society of Anesthesiologists status III-V) anaesthetized for laparotomy. METHODS: Horses were premedicated with intravenous (IV) xylazine (0.4-0.6 mg kg-1), anaesthesia was induced with midazolam (0.06 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV) and maintained with isoflurane in oxygen using volume-controlled ventilation without positive end-expiratory pressure. If PaO2 was < 100 mmHg (13.3 kPa), either a CPAP-M (50 cmH2O for 45 seconds) or salbutamol (0.002 mg kg-1) was administered. The intervention was considered successful if PaO2 reached 100 mmHg (13.3 kPa). If PaO2 remained < 100 mmHg (13.3 kPa), treatments were switched. PaO2/FiO2 ratio and estimated shunt fraction (F-shunt) were derived from data obtained from arterial blood gas measurements. Dynamic compliance (Cdyn) was calculated from variables recorded at the moment of arterial blood analysis. Fisher's exact tests compared success rates between treatments, and linear models were performed to test whether the treatment modified the values of the measurements; p < 0.05. RESULTS: Salbutamol was the first intervention in 28 horses and was effective in 22 horses. CPAP-M was the first intervention in 34 horses and was effective in 26 horses. CPAP-M after salbutamol was performed in six horses, with four responders, and salbutamol after CPAP-M was administered to eight horses, with one responder. Salbutamol, but not CPAP-M, significantly decreased F-shunt. Both salbutamol and CPAP-M significantly increased Cdyn. CONCLUSIONS AND CLINICAL RELEVANCE: Salbutamol and CPAP-M were comparably effective in improving oxygenation and Cdyn in anaesthetized horses with PaO2 < 100 mmHg (13.3 kPa). Whether combining both treatments might be beneficial needs to be confirmed on a larger number of horses.

Reversible Formation of a Light-Responsive Catalyst by Utilizing Intermolecular Cooperative Effects.

A photoresponsive system where structure formation is coupled to catalytic activity is presented. The observed catalytic activity is reliant on intermolecular cooperative effects that are present when amphiphiles assemble into vesicular structures. Photoresponsive units within the amphiphilic pre-catalysts allow for switching between assembled and disassembled states, thereby modulating the catalytic activity. The ability to reversibly form cooperative catalysts within a dynamic self-assembled system represents a conceptually new tool for the design of complex artificial systems in water.

Substrate-Induced Self-Assembly of Cooperative Catalysts.

Dissipative self-assembly processes in nature rely on chemical fuels that activate proteins for assembly through the formation of a noncovalent complex. The catalytic activity of the assemblies causes fuel degradation, resulting in the formation of an assembly in a high-energy, out-of-equilibrium state. Herein, we apply this concept to a synthetic system and demonstrate that a substrate can induce the formation of vesicular assemblies, which act as cooperative catalysts for cleavage of the same substrate.

Use of cis-atracurium to maintain moderate neuromuscular blockade in experimental pigs.

OBJECTIVE: To determine the dose of cis-atracurium needed to produce a moderate neuromuscular blockade (NMB) in pigs. STUDY DESIGN: Prospective experimental study. ANIMALS: Seven pigs [five females and two males; median (range) body weight: 47 (36-64) kg]. METHODS: Pigs were premedicated with intramuscular midazolam (0.3 mg kg-1) and ketamine (7 mg kg-1). Anaesthesia was induced with intravenous (IV) propofol 3 (1-4) mg kg-1 and maintained with isoflurane in oxygen. Based on a preliminary study, the subjects were administered 0.3 mg kg-1 cis-atracurium followed by 0.48 mg kg-1 hour-1 constant rate infusion (CRI) IV. A moderate NMB was defined as a train-of-four (TOF) count of ≤2 by acceleromyography. When the TOF count was >2, 0.1 mg kg-1 cis-atracurium was administered and the CRI was increased. The cis-atracurium CRI was decreased when the TOF count was under 2 for more than 15 minutes. The total dose of cis-atracurium required to maintain a moderate NMB was calculated as the total amount of cis-atracurium used (both CRI and supplementary boluses) divided by the administration time. RESULTS: The cis-atracurium CRI lasted for 87 (76-151) minutes. To induce and maintain a moderate neuromuscular blockade, the initial dose of cis-atracurium was 0.3 (0.3- 0.5) mg kg-1 and the CRI was 0.71 (0.37-0.98) mg kg-1 hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: The doses described in our study may help researchers obtain a moderate NMB using cis-atracurium in pigs.

Analytical Performance Evaluation of the New GEM® Premier™ 5000 in Comparison to the Epoc® Blood Gas Analyzer in Horses.

Different blood gas analyzers are used in equine practice. Every machine needs to be validated, as they have not been designed for use in horses. The aim of this study was to compare the newly marketed GEM5000 machine to the formerly validated epoc machine for blood gas analysis in horses. In this prospective, non-blinded, comparative laboratory analyzer study, 43 equine blood samples were analyzed on both analyzers and values were compared between the two machines via Lin's concordance analysis, Passing-Bablok regression analysis and Bland-Altman plots. Duplicate measurements were conducted on the GEM5000 machine to evaluate precision. The GEM5000 failed to achieve the required precision for tHb, Hct and iCa2+, but achieved acceptable precision for all other parameters. Concordance correlation analysis revealed poor correlation for Na+, Cl-, iCa2+, K+, Hct and tHb, while there was an at least moderate agreement for all other parameters. Passing-Bablok regression revealed significant constant bias for pCO2, pO2, Cl-, and iCa2+ and significant proportional bias for pCO2, iCa2+ and SO2. Bland-Altman analysis revealed significant systematic bias for Na+, Cl-, iCa2+, K+, Hct, tHb and SO2. This study shows that while precision of the GEM5000 is good, values should not be used interchangeably with data obtained from other blood gas analyzers.

Bioactive surface coating for preventing mechanical heart valve thrombosis.

BACKGROUND: Prosthetic heart valves are the only treatment for most patients with severe valvular heart disease. Mechanical valves, made of metallic components, are the most long-lasting type of replacement valves. However, they are prone to thrombosis and require permanent anticoagulation and monitoring, which leads to higher risk of bleeding and impacts the patient's quality of life. OBJECTIVES: To develop a bioactive coating for mechanical valves with the aim to prevent thrombosis and improve patient outcomes. METHODS: We used a catechol-based approach to produce a drug-releasing multilayer coating adherent to mechanical valves. The hemodynamic performance of coated Open Pivot valves was verified in a heart model tester, and coating durability in the long term was assessed in a durability tester producing accelerated cardiac cycles. Coating antithrombotic activity was evaluated in vitro with human plasma or whole blood under static and flow conditions and in vivo after surgical valve implantation in a pig's thoracic aorta. RESULTS: We developed an antithrombotic coating consisting of ticagrelor- and minocycline-releasing cross-linked nanogels covalently linked to polyethylene glycol. We demonstrated the hydrodynamic performance, durability, and hemocompatibility of coated valves. The coating did not increase the contact phase activation of coagulation, and it prevented plasma protein adsorption, platelet adhesion, and thrombus formation. Implantation of coated valves in nonanticoagulated pigs for 1 month efficiently reduced valve thrombosis compared with noncoated valves. CONCLUSION: Our coating efficiently inhibited mechanical valve thrombosis, which might solve the issues of anticoagulant use in patients and the number of revision surgeries due to valve thrombosis despite anticoagulation.

Effects of magnesium ions on two EMCV IRES key activity fragments.

Using NMR magnetization transfer from water and ammonia-catalyzed exchange of the imino protons, changes have been monitored in base-pair kinetics induced by Mg(2 + ) in two key activity fragments r(CACCUGGCGACAGGUG) and r(GGCCAAAAGCC) of the encephalomyocarditis virus internal ribosome entry site. For r(CACCUGGCGACAGGUG), the addition of Mg(2 + ) reveals two types of base-pairs: r(U(545)·A) and r(G(546)·C), in the first category, have lifetimes only slightly higher in the presence of Mg(2 + ), whereas their dissociation constants are substantially reduced. This behavior has been termed proximal. The base-pairs r(G(553)·C) and r(G(554)·C), in the second category, have lifetimes substantially higher in the presence of Mg(2 + ), whereas their dissociation constants remain almost constant. This behavior has been termed distal. Mg(2 + ) has a specific effect on r(CACCUGGCGACAGGUG), the magnitude of which is progressively modulated from the proximal region of the 16-mer towards its distal region. For r(GGCCAAAAGCC), an intermediate behavior is found for base-pairs r(G(565)·C) and r(G(572)·C). Their lifetimes are slightly higher in the presence of Mg(2 + ) and their dissociation constants are significantly lower, a behavior resembling that of the 16-mer proximal region. These results indicate that Mg(2 + ) diffusively moves around r(GGCCAAAAGCC).

Effect of Fentanyl Infusion on Heart Rate Variability and Anaesthetic Requirements in Isoflurane-Anaesthetized Horses.

Controversy continues to surround the use of opioids in equine anaesthesia, with variable effects reported. This blinded clinical study aimed to investigate the influence of a low-dose fentanyl continuous rate infusion (CRI) on isoflurane requirements, parasympathetic tone activity (PTA), and anaesthetic parameters in horses during general anaesthesia. All of the twenty-two horses included in the research underwent a standard anaesthetic protocol. Eleven horses in the fentanyl group (Group F) received a loading dose of fentanyl at 6 µg/kg, followed by a CRI of 0.1 µg/kg/min during anaesthesia. A further 11 horses in the control group (Group C) received equivalent volumes of normal saline. Anaesthetic parameters and PTA index were recorded during anaesthesia. The achieved mean fentanyl plasma concentration was 6.2 ± 0.83 ng/mL. No statistically significant differences between groups were found in isoflurane requirements, MAP values, and mean dobutamine requirements. However, horses in Group F required a significantly lower dose of additional ketamine to maintain a sufficient depth of anaesthesia. Significantly higher PTA values were found in the fentanyl group. Further research is warranted to determine the limitations of PTA monitoring, and the influence of various anaesthetics on its values.

Life-Threatening Hemorrhage During Patent Ductus Arteriosus Ligation in a Cat: Xenotransfusion With Canine Blood.

A 13-month-old Sphynx cat was referred for patent ductus arteriosus (PDA) ligation. A left thoracotomy was performed and the PDA was efficiently ligated. Immediately after chest tube placement, it presented extensive intrathoracic bleeding from the caudal intercostal artery. In view of the absolute necessity of a blood transfusion and given that compatible feline blood was not available, xenotransfusion of canine blood was administered to the cat and resulted in a positive outcome.

Influence of pesticide concentration on their heterogeneous atmospheric degradation by ozone.

A fraction of the atmospheric pesticides can be adsorbed on particles surface according to their physicochemical properties. After adsorption, pesticides can undergo heterogeneous reactivity with atmospheric oxidants such as ozone, but the influence of the pesticide surface coating (i.e., the percentage of the particle surface covered by pesticide molecules) on the degradation kinetics is not well-understood. To estimate the importance of this phenomenon, the influence of the surface coating level in pesticides on the heterogeneous ozonolysis of cyprodinil, deltamethrin, permethrin, and pendimethalin adsorbed on hydrophobic and hydrophilic silicas was investigated. Surface coating level varied from 0.3% to 15% of a monolayer. Generally, the increase of the surface coating level induced a slower degradation of the pesticides above 1%-3% of a monolayer. This decrease was attributed to a shielding effect. More aggregates of pesticides form with increasing surface coating leading to lower accessibility for ozone to the adsorbed pesticide molecules. Moreover, it was observed that the particle type could play a role in the influence of the surface coating level on the degradation rates. Results obtained will contribute to a better understanding of the atmospheric fate of pesticides and semi-volatile organic compounds in the particulate phase and show the importance of working with consistent surface coating level in order to compare the obtained degradation constants.

Retrospective evaluation of clinical use of cis-atracurium in horses.

BACKGROUND: To the authors' knowledge, there are no reports describing the use of cis-atracurium in the horse. OBJECTIVE: To describe the onset time and the duration of the neuromuscular blockade (NMB) of three different doses of cis-atracurium in horses and to determine the appropriate dose needed maintain a NMB. STUDY DESIGN: Retrospective study. METHODS: Horses which received cis-atracurium as part of a balanced anaesthetic protocol at the Equine Teaching Hospital of the University of Liège between March 2014 and June 2017 were included in this study. A train-of-four (TOF) stimulation pattern was used to assess the NMB. The cis-atracurium induction dose, the onset and duration of action (when TOF count was under three twitches) of the first bolus, the number of supplementary boluses of cis-atracurium and the total dose of cis-atracurium administered per horse, the total duration of the NMB and the recovery time were recorded and analysed. Also the use of an antidote and any side effects produced by cis-atracurium were recorded. RESULTS: From 37 horses that received cis-atracurium during this period, only 23 had a complete records and were included in the study. Three different doses of cis-atracurium were used to induce NMB: 100 µg/kg (n = 8) 75 µg/kg (n = 3) and 50 µg/kg (n = 12). Cis-atracurium 50 µg/kg failed to induce NMB in 3 horses. The onset of action was not significantly different between the three doses (5 minutes). The duration of the NMB was dose-dependent. The calculated dose of cis-atracurium necessary to maintain a NMB was 2.3 µg/kg/minute based on the sum of the induction dose and the supplementary boluses divided by the duration of the NMB. MAIN LIMITATIONS: A further prospective study is needed to confirm the results. CONCLUSIONS: Cis-atracurium can be an alternative to other NMBA in horses.

Prolonged Recovery From General Anesthesia Possibly Related to Persistent Hypoxemia in a Draft Horse.

Horses are susceptible to developing large areas of pulmonary atelectasis during recumbency and anesthesia. The subsequent pulmonary shunt is responsible for significant impairment of oxygenation. Since ventilation perfusion mismatch persists into the post-operative period, hypoxemia remains an important concern in the recovery stall. This case report describes the diagnosis and supportive therapy of persistent hypoxemia in a 914 kg draft horse after isoflurane anesthesia. It highlights how challenging it can be to deal with hypoxemia after disconnection from the anesthesia machine and how life-threatening it can become if refractory to treatment. Furthermore, it stresses the point on the interactions between hypoxemia and other factors, such as residual drug effects and hypothermia, that should also be considered in the case of delayed recovery from general anesthesia.

Substrate-Induced Self-Assembly of Cooperative Catalysts.

Dissipative self-assembly processes in nature rely on chemical fuels that activate proteins for assembly through the formation of a noncovalent complex. The catalytic activity of the assemblies causes fuel degradation, resulting in the formation of an assembly in a high-energy, out-of-equilibrium state. Herein, we apply this concept to a synthetic system and demonstrate that a substrate can induce the formation of vesicular assemblies, which act as cooperative catalysts for cleavage of the same substrate.