Correlation of Sedline-generated variables and clinical signs with anaesthetic depth in experimental pigs receiving propofol.

Most of currently available electroencephalographic (EEG)-based tools to assess depth of anaesthesia have not been studied or have been judged unreliable in pigs. Our primary aim was to investigate the dose-effect relationship between increasing propofol dose and variables generated by the EEG-based depth of anaesthesia monitor Sedline in pigs. A secondary aim was to compare the anaesthetic doses with clinical outcomes commonly used to assess depth of anaesthesia in this species. Sixteen juvenile pigs were included. Propofol infusion was administered at 10 mg kg-1 h-1, increased by 10 mg kg-1 h-1 every 15 minutes, and stopped when an EEG Suppression ratio >80% was reached. Patient state index, suppression ratio, left and right spectral edge frequency 95%, and outcomes from commonly used clinical methods to assess depth of anaesthesia in pigs were recorded. The best pharmacodynamic model was assessed for Patient state index, suppression ratio, left and right spectral edge frequency 95% in response to propofol administration. The decrease of Patient state index best fitted to an inhibitory double-sigmoid model (including a plateau phase). The increase of suppression ratio fitted a typical sigmoid Emax model. No relevant relationship could be identified between spectral edge frequency 95% values and propofol administration. A large variability in clinical outcomes was observed among pigs, such that they did not provide a reliable evaluation of propofol dose. The relationship between propofol dose and Patient state index/suppression ratio described in the present study can be used for prediction in future investigations. The evaluation of depth of anaesthesia based on common clinical outcomes was not reliable

Intubation in Swine: What Recumbency to Choose?

Endotracheal intubation (ETI) is challenging in pigs. We compared the number of attempts and time to perform ETI, and the subjective perception of ease, while the animal was positioned in dorsal (DR) or sternal (SR) recumbency, as well as assessed whether operator experience influences the outcome. Participants were divided into three groups: undergraduates (ST; veterinary students), graduates (GR; veterinarians without specific anaesthesia training) and experts (EX; veterinary anaesthesia intern/resident and diplomate of the European College of Veterinary Anaesthesia and Analgesia). Each participant intubated one freshly euthanised pig in DR and ST. Number of attempts and time to correctly perform ETI, number of oesophageal intubations and answers to Likert-scale questions on larynx visualization and ease of endotracheal tube introduction and advancement were recorded. Thirty-three participants were enrolled (15 ST, 10 GR and 8 EX). Less attempts (p = 0.002) and time (p = 0.002) to correctly perform ETI were needed in SR for the ST group. In 21/119 and 5/48 ETI attempts, oesophageal intubation was performed in DR and SR, respectively. Larynx visualization (p < 0.001) and endotracheal tube introduction (p < 0.001) were perceived as easier in SR for the ST group. No difference between recumbencies was found in perceived ease to advance the endotracheal tube. For inexperienced operators, intubation in SR can be recommended

A pilot investigation of the efficacy and safety of magnesium chloride and ethanol as anesthetics in Loligo vulgaris embryos.

The inclusion of cephalopods in the legislation related to the use of animals for experimental purposes has been based on the precautionary principle that these animals have the capacity to experience pain, suffering, distress, and lasting harm. Recent studies have expanded this view and supported it. Handling cephalopod mollusks in research is challenging and whenever more invasive procedures are required, sedation and/or anesthesia becomes necessary. Therefore, finding adequate, safe, and effective anesthetics appears mandatory. Several substances have been considered in sedating cephalopods, in some instances applying those utilized for fish. However, species-specific variability requires more detailed studies. Despite long-lasting experience being linked to classic studies on squid giant axons, evidence of action on putative anesthetic substances is scarce for Loligo vulgaris and particularly for their embryos. The aim of the current study was to evaluate effects elicited by immersion of squid embryos in anesthetic solutions and examine whether these forms display a similar reaction to anesthetics as adults do. Different concentrations of ethanol (EtOH; 2, 2.5, and 3%) and magnesium chloride (MgCl2; 1, 1.5, and 1.8%) were tested by adopting a set of indicators aimed at exploring the physiological responses of squid embryos. Forty-two embryos of the common squid Loligo vulgaris (stages 27-28) were assigned to three conditions (EtOH, MgCl2, and controls) and video recorded for 15 min (5 min before, 5 min during, and 5 min after immersion in the anesthetic solutions). In each group, the heart rate, respiratory rate, buoyancy, chromatophore activity, and tentacles/arms responses were assessed to evaluate the embryos' vitality and responsiveness to stimulation. Both substances provoked a decrease in heart and respiratory rates and inhibited buoyancy, chromatophores, and tentacles/arms responses; no adverse effects were observed. EtOH had a faster onset of action and faster recovery than MgCl2, being potentially more adequate as an anesthetic for shorter procedures. Even though MgCl2 caused a longer muscle relaxation, the reversibility was not confirmed for the 1.8% concentration; however, lower concentrations triggered similar results as the ones obtained with the highest EtOH concentrations. We have shown that the late developmental stages of Loligo vulgaris embryos could represent a good model to evaluate anesthetics for cephalopods since they can display similar reactions to anesthetics as adults animals do

Anaesthetic Management of a Labrador Retriever Undergoing Adrenalectomy for Phaeochromocytoma Excision, a Case Report.

Perioperative management of cases undergoing phaeochromocytoma removal should aim at normalising blood pressure and heart rate, restoring volume depletion, and preventing catecholamine release induced by surgical manipulation. In this case report, a novel pharmacological approach in a dog undergoing surgical tumour excision is described. A 7-year-old 25-kg spayed female Labrador Retriever presented for repeated episodes of generalised weakness, pale mucous membranes, tachycardia, tremor, panting, vomiting, and hypertension over the last month was referred for surgical treatment of a left-sided adrenal tumour with invasion of the caudal vena cava. Severe hypertensive episodes occurred repeatedly, starting early during the anaesthetic period, while clipping and cleaning the abdominal area, and continued intraoperatively when the tumour was handled. Moderate hypotension occurred once the tumour was isolated and worsened during temporary caudal vena cava flow interruption and cavotomy. The patient was treated preoperatively with phenoxybenzamine to prevent hypertensive crises. Intraoperatively, magnesium sulphate and urapidil were used to control blood pressure. This treatment was effective in reducing the magnitude of blood pressure spikes but not sufficient to prevent hypertensive peaks, especially during tumour manipulation. Hypotension was treated with synthetic colloid and crystalloid boli, and noradrenaline continuous infusion. Blood transfusion was performed in response to acute bleeding during cavotomy. The dog recovered successfully from anaesthesia and its quality of life was deemed excellent by the owner at the last follow up, 22 months after surgery. The histopathology confirmed the diagnosis of phaeochromocytoma with an invasion of the phrenicoabdominal vein. In the present case, we obtained a successful outcome but failed to provide haemodynamic stability throughout the procedure

Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration

BACKGROUND: Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictable. The aim of this case report is to describe the pharmacological profile of morphine and its metabolites after prolonged epidural administration in a pregnant mare and her foal. CASE PRESENTATION: A 20 years old pregnant mare was presented to our hospital because of severe lameness, 2 months before delivery. Following an ineffective systemic pain treatment, an epidural catheter was inserted and morphine administered (initial dose 0.1 mg/kg every 8 h). Due to its efficacy in controlling pain, it was continued until end of gestation. Plasmatic concentration of morphine and its metabolites were assessed in the mare 6 weeks after starting the treatment, and in both the mare and foal during the first days after delivery. Plasmatic values similar to those previously reported in the literature following morphine short term administration through various routes and not accompanied by side effects were found in the mare, except during an excitatory period. Moreover, no evidence of dangerous drug accumulation or significant milk passage was noticed in the foal. Mild reduction of feces production with no signs of colic and two self-limiting episodes of excitement occurred during treatment in the mare. No side effects occurred during gestation and first phases of life in the foal. CONCLUSION: Prolonged epidural administration of morphine in a pregnant mare allowed good pain control in absence of clinically relevant side effects, in both the mare and her foal. Sudden increase in morphine plasmatic concentration can occur and side effects appear; careful treatment to the lowest effective dose and continuous monitoring of the clinical condition of the treated horse should be performed. KEYWORDS: Epidural; Foal; Horse; Morphine; Morphine-3-glucuronide; Morphine-6-glucuronide; Pregnanc

Induction of general anaesthesia by blowpipe darting in a fractious companion horse

a fractious nine-year-old, 520-kg, neutered Swiss Warmblood was presented with a history of anorexia, progressive weight loss and mild hindlimb lameness. Because of its temperament, standard physical examination was considered to be only feasible under general anaesthesia. For safety reasons, general anaesthesia was planned to be induced by blowpipe darting. two attempts are described and discussed in the present report. the first attempt, using a combination of medetomidine and tiletamine-zolazepam, was unsuccessful. Conversely, detomidine combined with butorphanol, followed by a second dart of detomidine and tiletamine-zolazepam, proved to be adequate to induce anaesthesia. Factors that could have influenced the outcome, such as different therapeutic approach, drug protocol and dosages, stress level, or genetic mutations, are presented and discussed

Pharmacokinetic-pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses

OBJECTIVE To evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration. STUDY DESIGN Prospective, experimental, nonrandomized trial. ANIMALS A total of 10 healthy adult warmblood horses. METHODS Romifidine (loading dose: 0.08 mg kg-1, infusion: 0.03 mg kg-1 hour-1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic-pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested. RESULTS A two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33). CONCLUSIONS AND CLINICAL RELEVANCE Romifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration

Is a Block of the Femoral and Sciatic Nerves an Alternative to Epidural Analgesia in Sheep Undergoing Orthopaedic Hind Limb Surgery? A Prospective, Randomized, Double Blinded Experimental Trial

Peripheral nerve blocks are commonly used in human and veterinary medicine. The aim of the study was to compare the analgesic efficacy of a combined block of the femoral and sciatic nerves with an epidural injection of ropivacaine in experimental sheep undergoing orthopaedic hind limb surgery. Twenty-five sheep were assigned to two groups (peripheral nerve block; sciatic and femoral nerves (P); epidural analgesia (E)). In group P 10 mL ropivacaine 0.5% was injected around the sciatic and the femoral nerves under sonographic guidance and 10 mL NaCl 0.9% into the epidural space while in group E 10 mL ropivacaine 0.5% was injected into the epidural space and 10 mL NaCl 0.9% to the sciatic and the femoral nerves. During surgery, heart rate, respiratory rate and mean blood pressure were used as indicators of nociception. In the postoperative phase, nociception was evaluated every hour by use of a purposefully adapted pain score until the animal showed painful sensation at the surgical site. The mean duration of analgesia at the surgical wound was 6 h in group P and 8 h in group E. Mean time to standing was 4 h in group P and 7 h in group E. In conclusion time to standing was significantly shorter in group P while the duration of nociception was comparable in both groups. The peripheral nerve block can be used as an alternative to epidural analgesia in experimental sheep

Usefulness and Reliability of the Bispectral Index during Balanced Anesthesia for Neurovascular Surgery in New Zealand White Rabbits

Few data about the electroencephalogram and its calculated indices, such as the bispectral index (BIS), have been reported in rabbits. We aimed to evaluate whether a clinically stable anesthesia was mirrored by consistent and stable BIS values and to investigate the effects of modified cerebral blood supply, due to bilateral carotid clamping and re-opening, on BIS values. We also investigated the effects of fentanyl, as an antinociceptive drug, on the BIS. Sixty-eight rabbits undergoing general anesthesia for surgical creation of carotid bifurcation aneurysms were enrolled. The BIS values were recorded at nine selected time points (TPs) during each procedure and before and after fentanyl administration. The BIS values over time were compared with two-way repeated-measures analysis of variance followed by Tukey test, while the Wilcoxon signed rank test was performed to compare values at clamping and re-opening of the carotids as well as before and after fentanyl administration. The BIS values were significantly lower during anesthesia than at the end of anesthesia and at tracheal extubation; no significant differences were found among other TPs. Adequate depth of anesthesia was mirrored by consistent BIS values among rabbits, and alteration of cerebral blood supply did not modify BIS values, except once. Following fentanyl, BIS values did not change in a clinically relevant way

Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles.

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45 min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC-MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%-56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1 ) and central and peripheral volumes of distribution (V1 , V2 ). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs