Postoperative opioid-free analgesia in dogs undergoing tibial plateau leveling osteotomy: a feasibility study.

Objectives: This study was designed to prospectively evaluate the feasibility of an opioid-free anesthesia protocol and describe the quality of recovery and management of postoperative analgesia in dogs after a tibial plateau leveling osteotomy (TPLO). Methods: In total, 20 dogs presented for TPLO were included. After premedication with intravenous (IV) medetomidine (0.005-0.007 mg/kg) and midazolam (0.2 mg/kg), the dogs were anesthetized using ketamine (2 mg/kg) and propofol and maintained with isoflurane and ketamine CRI (0.6 mg/kg/h). Sciatic and femoral nerve blocks were performed with bupivacaine 0.5% (0.087 +/- 0.01 and 0.09 +/- 0.02 mL/kg, respectively). Meloxicam (0.2 mg/kg IV) was administered intraoperatively, after osteotomy. Fentanyl (0.002 mg/kg IV) was administered intraoperatively, as rescue analgesia in the case of sustained increase in cardiorespiratory variables. Two pain scores (French 4A-VET and Glasgow short form) were performed at conscious sternal recumbency and 2, 4, 6, 8, 12, and 20 h after extubation and compared to baseline using a Friedman test followed by a Nemenyi post-hoc test. The time taken for the first food intake and urination was reported. Results: Intraoperative opioid-free anesthesia was feasible in 11 dogs, whereas 9 dogs received fentanyl once during arthrotomy. No opioid postoperative rescue analgesia was required. Food intake occurred within 6 h, and all dogs were discharged after 24 h without any complication. Conclusion: Total opioid-free postoperative analgesia was achieved in all dogs, with adequate recoveries. Although opioid-free anesthesia was feasible in 55% of the population, a single dose of fentanyl was necessary in 45% of the dogs during arthrotomy.

Evaluation of pimobendan effect on sublingual microcirculation in an experimental pharmacology induced hypotension porcine model.

New therapeutic approaches are needed to simultaneously resuscitate macro- and microcirculation during circulatory shock. The aims of this study were to explore the microcirculatory and macrocirculatory effects of pimobendan, an inodilator with dual phosphodiesterase 3 inhibitor and calcium-sensitizing effects, in an experimental porcine model of pharmacologically induced hypotension associating vasoplegia and decreased cardiac output. Eight piglets were anesthetized and monitored for their hemodynamic parameters. Hypotension was induced by sevoflurane overdose until a mean arterial pressure between 40 and 45 mmHg was reached. A bolus of pimobendan (0.25 mg/kg) was administered intravenously thereafter. Sublingual microcirculation was evaluated using a Sidestream Dark Field imaging device. Hemodynamic and microcirculatory parameters were recorded at the baseline period (A), immediately before pimobendan administration (B) and after pimobendan administration (C). Induction of hypotension was associated with a decreased cardiac index and microcirculation alterations. Pimobendan administration was associated with a significant increase in heart rate, cardiac index and decrease in systemic vascular resistance index. A significant increase in proportion of perfused vessels for all vessels (+8%, [2; 14], P = 0.01) and small vessels (+8% [1; 14], P = 0.03), in microvascular flow index (+0.31 AU, [0.04; 0,58], P = 0.03) were noticed, as well as a decrease in heterogeneity index (-0.34 [-0.66; -0.03], P = 0.04) and De Backer score for all vessels (-1.04, [-1.82; -0.25], P = 0.02). In conclusion, in a simple model of pharmacologically induced hypotension, pimobendan was associated with an improvement in several microcirculatory parameters.

Heated intravenous fluids alone fail to prevent hypothermia in cats under general anaesthesia.

Objectives The objective was to evaluate the clinical efficiacy of a constant rate infusion of heated fluid as the sole means of preventing intraoperative hypothermia in cats. Methods This randomised, prospective, clinical study was conducted at a university teaching veterinary hospital. Female cats (American Society of Anesthesiologists [ASA] grade I) undergoing elective surgery by laparotomy under general anaesthesia (acepromazine 0.05 mg/kg SC; morphine 0.2 mg/kg IV; propofol IV titrated, isoflurane 2% in 100% oxygen) were randomised in two groups. Both groups were infused with fluid (NaCl 0.9%, 5 ml/kg/h) either at room temperature (control group) or prewarmed at 43°C (warmed group) using an Astoflo Plus eco (Stihler Electronic) fluid heating device. No other heating device was used. Temperature, heart rate, respiratory rate and SpO2 were evaluated after induction (T0) and every 15 mins for 1 h (T15, T30, T45, T60). Mean arterial blood pressure was recorded every 30 mins (T0, T30 and T60). Results Thirty-four female cats (ASA grade I) were enrolled in the study. There was no difference in age, weight, propofol dose or room temperature (22.4 ± 1.1°C vs 22.0 ± 1.5°C; P = 0.363) between control and warmed groups, respectively. In both groups, oesophageal temperature significantly decreased during anaesthesia ( P <0.0001). The temperature decrease after 1 h was -3.6 ± 0.7°C in the warmed group and was not significantly different from the control group (-3.4 ± 0.7°C; P = 0.307). The slopes of the temperature decrease did not significantly differ between the two groups (-0.058 ± 0.013°C/min vs -0.060 ± 0.010°C/min for the control and warmed groups, respectively; P = 0.624). Conclusions and relevance This study provides clinical evidence that a constant rate infusion of heated fluid alone fails to prevent intraoperative hypothermia in cats. The low infusion rate (5 ml/kg/h) could partly explain the ineffectiveness of this active warming device in minimising or delaying the onset of intraoperative hypothermia.

Novel chemometric strategy based on the application of artificial neural networks to crossed mixture design for the improvement of recombinant protein production in continuous culture.

The optimal blends of six compounds that should be present in culture media used in recombinant protein production were determined by means of artificial neural networks (ANN) coupled with crossed mixture experimental design. This combination constitutes a novel approach to develop a medium for cultivating genetically engineered mammalian cells. The compounds were collected in two mixtures of three elements each, and the experimental space was determined by a crossed mixture design. Empirical data from 51 experimental units were used in a multiresponse analysis to train artificial neural networks which satisfy different requirements, in order to define two new culture media (Medium 1 and Medium 2) to be used in a continuous biopharmaceutical production process. These media were tested in a bioreactor to produce a recombinant protein in CHO cells. Remarkably, for both predicted media all responses satisfied the predefined goals pursued during the analysis, except in the case of the specific growth rate (mu) observed for Medium 1. ANN analysis proved to be a suitable methodology to be used when dealing with complex experimental designs, as frequently occurs in the optimization of production processes in the biotechnology area. The present work is a new example of the use of ANN for the resolution of a complex, real life system, successfully employed in the context of a biopharmaceutical production process.