Plasma concentrations of Tapentadol and clinical evaluations of a combination of Tapentadol plus Sevoflurane for surgical anaesthesia and analgesia in rabbits (Oryctolagus cuniculus) undergoing orchiectomy

Pain is probably under-treated in animals, particularly in rabbits, due to a lack of familiarity with the species and limited information about analgesic dose, efficacy and safety. Tapentadol (TAP) is a novel opioid drug, with a proven efficacy and safety profile in humans, which could be useful as an analgesic in rabbits. In a clinical study, TAP was administered (5 mg/kg, IV) to seven male New Zealand White rabbits 5 min before anaesthetic induction with sevoflurane to perform orchiectomy. Monitoring of vital signs, including heart rate, electrocardiogram, respiratory rate, invasive blood pressure, oxygen saturation, righting reflex, palpebral reflex, jaw tone and tongue retraction, was performed throughout surgery. Pain was assessed for 8 h following surgery, using previously validated parameters, physiological assessments and behavioural assessments. Blood was also collected at regular intervals to assess the pharmacokinetic profile of the drug. TAP was rapidly distributed and eliminated in rabbits. Apnoea did not occurred in any subject. Following surgery, there were very few observable signs of pain in four rabbits and all resumed normal activities within a few hours. In conclusion, this is the first study about the clinical effects and potential utility of TAP as an adjunct drug for anaesthesia and analgesia in the rabbit. However, further studies are still needed before its use in the veterinary clinical practice

Supramolecular networks stabilise and functionalise black phosphorus

The limited stability of the surface of black phosphorus (BP) under atmospheric conditions is a significant constraint on the exploitation of this layered material and its few layer analogue, phosphorene, as an optoelectronic material. Here we show that supramolecular networks stabilised by hydrogen bonding can be formed on BP, and that these monolayer-thick films can passivate the BP surface and inhibit oxidation under ambient conditions. The supramolecular layers are formed by solution deposition and we use atomic force microscopy to obtain images of the BP surface and hexagonal supramolecular networks of trimesic acid and melamine cyanurate (CA.M) under ambient conditions. The CA.M network is aligned with rows of phosphorus atoms and forms large domains which passivate the BP surface for more than a month, and also provides a stable supramolecular platform for the sequential deposition of 1,2,4,5-tetrakis(4-carboxyphenyl)benzene to form supramolecular heterostructures

Methadone and Dexmedetomidine combination as premedicant for ovariectomy and orchiectomy in cat

The aim of the study was to evaluate sedation level and analgesic efficacy produced by the association of methadone 0.5 mg/kg and dexmedetomidine 5 mcg/kg for neutering surgery in cats. Thirty client‐owned cats (8 males and 22 females) anaesthetised for elective neutering surgery, considered healthy on the basis of clinical exam and haematological tests, were enrolled in the study. Cats were premedicated with dexmedetomidine 5 mcg/kg and methadone 0.5 mg/kg administered intramuscularly. Cats were then induced with propofol, intubated and maintained with isoflurane in 100% oxygen. Time to reach the sedative effects wasregistered as well as the following clinical parameters: heart rate (HR), systolic arterial pressure, using the doppler technique (SAP), respiration rate (RR), end tidal CO2 (EtCO2), haemoglobin oxygen saturation (SpO2), temperature (T°) and end tidal isoflurane percentage (EtIso). All the parameters were recorded every five minutes until the end of anaesthesia. Three different simple descriptive four points scales were used to evaluate the degree of sedation after premedication, the catheter placement and the quality of recovery after general anaesthesia (Bortolami et.al 2011), starting from 0 (no sedation, difficult catheter placement, poor recovery) to 3 (profound sedation, very easy catheter placement, excellent recovery). Mean time to reach the maximum sedation level was 4 ± 5 minutes; median sedation score resulted 2 (0‐3), median catheter placement score was 3 (0‐3) and median recovery quality score was 3 (0‐3). Mean dosage of propofol for intubation resulted 1.6 ± 1 mg/kg. EtIso during the surgery variated from 0.83 to 1.4 %. Nine of the 30 cats (30%) in the study required fentanyl rescue analgesia during the surgery; one cat received dopamine infusion as hypotension treatment; 6 cats received assisted mechanical ventilation and 1 cat received controlled mechanical ventilation. The association of dexmedetomidine 5 mcg/kg and methadone 0.5 mg/kg resulted in an overall good quality sedation with some exception: in fact 3 cats presented a poor sedation score (0‐1), nevertheless the score for the catheter placement was always 2 or more. The onset of the sedation was quite fast and the association of drugs resulted in propofol dose‐sparing effect. A high percentage of patients required rescue pain management during surgery showing inadequate analgesia in those cases. In conclusion premedication with methadone 0.5 mg/kg and dexmedetomidine 5 mcg/kg given intramuscularly, resulted in a good combination drug protocol which allow to handle cats easily and the use of low‐dose propofol for anaesthesia induction; however the analgesia obtained was not always adequate

UWB Pulse Propagation into Layered Model of Human Body

The biomedical applications of Ultra-Wide Band (UWB) radar system promise a very important means to remotely monitor physiological signal. Researchers have shown great interest in proposing analytical techniques to accurately predict the propagation of UWB pulse in tissues layers. This paper focuses the study of the propagation of a UWB pulse into a human body to characterize the absorption and reflection of UWB signal due to different layers. Several time behaviors for the reflected pulse were used and compared with the transmitted pulse to the feasibility of movement and heartbeat activity monitoring. Results from the simulation showed that if the UWB transmit antenna is placed far from the human body, the reflection from the interface between the air and the fat can be used to detect the movements of the activity. Therefore, we proposed designing an analytic model of tissue layers, considering some parameters. Furthermore, the frequency dependency of the different layers, tissues dielectric properties and the continuous motion of intra thoracic tissue layers were incorporated. The present work illustrates an application of UWB system for contactless detection and analysis of the human vital signal. This paper focuses on the design of a propagation UWB pulse into a layered model of the human body using the tool of modeling Agilent Advanced Design System

Sedative and Respiratory Effects of Intramuscular Detomidine and Butorphanol in Donkeys Sedated for Bronchoalveolar Lavage

The aim of this study was to evaluate the effects of intramuscular (IM) detomidine and butorphanol on sedation, arterial blood gases, and bowel motility in sixteen healthy Amiata donkeys undergoing bronchoalveolar lavage (BAL). Before administration of detomidine and butorphanol, baseline values for heart rate (HR), respiratory frequency (fr), rectal temperature, arterial blood gases, and sedation score (range 0–9) were recorded as Tbase and bowel motility was assessed. Sedation was assessed with a composite sedation scale. After IM injection of detomidine 0.06 mg kg−1and butorphanol 0.05 mg kg−1, HR, fr, temperature, and sedation score were registered every 5 minutes. Arterial blood was sampled when sedation score was greater than or equal to 6 right before performing the diagnostic procedure (T1) and at a sedation score of 3 or lower, which was considered the end of sedation (T2). Bowel motility was assessed every hour after the end of sedation. Sedation score of 6 or more was reached after 10 minutes in all animals. Mean sedation time was 38.8 ± 5.2 minutes. PaO2, HR, and fr were significantly lower at T1 and T2 compared to Tbase values. Fshunt significantly increased at T2, in comparison to Tbase. Time from injection to return to normal bowel motility was 272 ± 62 minutes. Intramuscular detomidine and butorphanol provided satisfactory sedation for BAL in donkeys, in terms of reliability and duration. Clinicians should be aware of the reduction of PaO2that can arise

EVALUATION OF MOST CARE® /PRAM VERSUS ECHOCARDIOGRAPHY FOR CARDIAC OUTPUT ESTIMATION IN DOGS: PRELIMINARY STUDY

Introduction Cardiac output monitoring in intensive care unit can reduce complications and mortality of critical patient. Non-invasive methods for cardiac output (CO) evaluation include ultrasonography and pulse contour techniques. The Most Care ®/Pram monitor permits cardiac output evaluation from a peripheral artery and can provide continuous measurements. The aim of this study was to evaluate the agreement between cardiac output measurements obtained with Most Care versus transthoracic echocardiography in dogs. Methods Ten healthy Labrador Retrievers of 8-12 month age, anaesthetized for diagnostic procedures were enrolled in the study. A written consensus was signed from the owners. Complete echocardiographic, hematological and biochemical analysis were performed before enrolling the animals in the study. An arterial catheter (20 G) was positioned in the right dorsal pedal artery of each dog after a local anesthetic cream (EMLA) was placed on for 20 minutes. Serial cardiac output measurements were done simultaneously with echocardiography and with Most Care, for each dog, before anesthesia (T0) and 5 minutes after induction of anesthesia (T5). During measurement dogs were positioned in right lateral recumbency and a pressure transducer was positioned at right atrium level on a specific support, which was isolated form the dog. The pressure transducer was connected to the monitor and to the patient with a three-way stopcock. Anesthesia was provided using 10 mg/kg of propofol IV. A Pearson parametrical correlation test was performed and r2 values were considered significant when P <0.05. Results Two measurements were recorded in each dog for each time point. Mean weight of the dogs was 30.4 ± 4.1 kg. Recorded echocardiographic and Most Care CO values are listed in the table. The values registered showed a good correlation between the two employed methods with a r2 of 0.52 for T0 values and of 0.68 for T5 values (P<0.0001 in both time points). Movements of the patient can alter the recorded values of Most Care and before anesthesia dogs had to be physically restrained in order to have correct values. Discussion - Conclusion This study confirmed a good correlation between the two employed methods for cardiac output evaluation. Those preliminary results are promising but need to be confirmed with larger population study. The possibility to have a validated pulse contour method for continuous cardiac output monitoring in intensive care unit or during anesthesia could be very important for the management of cardiovascular complication of critical patients. Further studies are needed to evaluate the effectiveness of this technique in the clinical setting and in patients of various weights

USE OF FENTANYL TRANSDERMAL SOLUTION OR METHADONE FOR PAIN CONTROL IN DOGS WITH ACUTE PANCREATITIS: PRELIMINARY STUDY

Introduction Pain management in patients with pancreatitis still appears problematic and complex. Recently a long-acting (96 hours) fentanyl transdermal solution (Recuvyra®) has been licensed for postoperative pain management in dogs. The aim of this study was to evaluate the analgesic efficacy of Recuvyra® in comparison with methadone during acute pancreatitis in dogs. Methods Twelve dogs with acute pancreatitis were enrolled in the study. Owners signed a consensus to enroll animal in the study. Dogs were randomly divided in two groups: one group received methadone (GM) (0.3 mg/kg, IV) and one group received fentanyl transdermal solution (GFT) at 2.6 mg/kg dosage. Both groups also received lidocaine 1 mg/kg IV followed by an infusion of 1-2 mg/kg/h for at least 48 hours. Because of the long onset of action (4 hours) the GFT received methadone (0.3 mg/kg IV) simultaneously with the transdermal solution application. Heart rate, respiratory rate, mean arterial pressure and temperature were recorded before the analgesic administration and after 4, 6, 8, 10, 12, 24, 32, 48 and 72 hours. Pain evaluation was done every 2 hours for the first twelve hours and every 4 hours until 72 hours, with a 4aVet pain scale. The operator in charge of pain assessment was unaware of the treatment done. When a score higher than 5 was recorded animals were treated with methadone IV 0.3 mg/kg (in GM) or 0.1 mg/kg (GFT) until a maximum dose of 0.6 mg/kg every 3 hours; the clinicians responsible for the drug administration were not the same assigned to the pain score evaluation. Results Two dogs (one for each group) were euthanized after 38 and 43 hours because of worsening of general conditions. All the surviving patients started eating after 32-48 from the beginning of therapy. Heart rate, in GFT, significantly decreased at T8 until T72 in comparison with T0. In GM pain score was significantly lower a T48 and T72 in comparison to T0, while in GFT scores recorded at T32, T48 and T72 were significantly lower in comparison to T0 (see table). No differences were recorded between the 2 groups. One dog of GFT received one dose of methadone 0.1 mg/kg IV. Mean dosage of methadone in GM was 0.53 ± 0.13 mg/kg every 3 hours. Discussion - Conclusion Recuvyra® was clinically effective in the control of pain during acute pancreatitis in dogs. Pain score decreased in both groups but in the GFT pain score was halved after 6 hours of treatment and only one dog needed rescue analgesia. The low number of cases could be the reason why significant differences were not detected between groups. In GFT a decrease of heart rate was recorded after eight hours from administration: it is not possible to differentiate between analgesic efficacy (disease resolution) and intrinsic vagotonic effect of fentanyl. A specific visceral pain scoring system does not exist for dogs and this could be an important limit of this study. Further studies are needed to verify the use of transdermal fentanyl solution (Recuvyra®) in dogs with pancreatitis

Perioperative analgesic effect of epidural ropivacaine 0.5% in dogs undergoing total monolateral mastectomy

Total mastectomy causes considerable tissue damage and a marked perioperative pain response. This study aimed to evaluate the effectiveness of epidural administration of 0.5% ropivacaine on pain management for mastectomy in dogs. Twenty client-owned dogs were enrolled and divided in 2 groups: Epi-group (received a single dose of 0.5% ropicavaine epidurally) and Mor-group (received morphine IM). All dogs were premedicated with 0.3 mg kg 1 of morphine IM, anaesthesia was induced and maintained with propofol infusions. The volume of ropivacaine was calculated with a specific nomogram (Otero et al, 2010). Records of HR, fR, MAP, PE’CO2 and SpO2 were taken before and after epidural administration and throughout surgery. On recovery, dogs received 2 mg kg 1 of robenacoxib SC and were evaluated for pain score every hour, for 20 hours, using the Glasgow short form pain scale. Intraoperative rescue analgesia with fentanyl 2 lg kg 1 was administered if HR and MAP increased over 20% from previous values. Postoperative rescue analgesia (morphine 0.3 mg kg 1 IM) was administered with pain score higher than 5. Data were analysed with ANOVA tests and Tukey post hoc was used to evaluate data all over the time; a Friedmann test was used to compare pain scores. Values of p < 0.05 were considered significant. No differences were detected between groups for age, weight and surgery time. All the dogs of Mor-group and three dogs in Epi-group required intraoperative fentanyl. Postoperative pain score was significantly higher in Mor-group (p = 0.03) and the morphine requirement, over 20 hours, was significantly higher (p = 0.004) for Mor-group (1.4 0.43 mg kg 1) compared to Epi-group (0.76 0.42 mg kg 1). Epidural administration of ropivacaine 0.5% was a good analgesic option and the nomogram to calculate the injected volume appeared satisfactory for this procedure

Proximal RUMM block in dogs: preliminary results of cadaveric and clinical studies

Objective: To design and assess the perioperative analgesic efficacy of an ultrasound (US)-guided radial (R), ulnar (U), median (M) and musculocutaneous (Mc) nerve blocks, performed together in the axillary space by a single, in-plane approach. Study design: Anatomical research and prospective clinical study. Animals: A group of three dog cadavers and 15 client-owned dogs undergoing orthopaedic thoracic limb surgery. Methods: Phase 1: Anatomical dissection and US study of the axillary space were performed to design the US-guided proximal RUMM block. The technique was considered successful if a total volume of 0.15 mL kg –1 new methylene blue solution completely stained the four nerves in two cadavers for ≥2 cm. Phase 2: In 15 client-owned dogs undergoing orthopaedic thoracic limb surgery, the RUMM block designed in phase 1 was performed to provide analgesia using a total volume of 0.15 mL kg –1 of ropivacaine 0.5%. The block was considered effective if the intraoperative fentanyl requirement was 2 cm. No intrathoracic dye spread was found. Phase 2: In 14/15 anaesthetized dogs, mean intraoperative fentanyl requirement was 0.25 ± 0.05 mcg kg –1 hour –1 . Postoperatively, all dogs had SF-GCMPS ≤5/20 up to 8 hours. Conclusions and clinical relevance: The US-guided proximal RUMM block performed at the axillary level with a single, in-plane needling approach using 0.15 mL kg –1 of ropivacaine 0.5% minimized fentanyl requirement during thoracic limb surgery, contributing to postoperative analgesia up to 8 hours after execution of the peripheral nerve block

ULTRASOUND AS A SUPPORT TOOL FOR CAUDAL EPIDURAL INJECTION IN THE HORSE

The aim of the study was to describe the sonoanatomy of the epidural space at first, second and third coccygeal space in horses. Phase 1: two tails, obtained from a slaughterhouse, were used to perform the ultrasound anatomical study of the epidural space at the coccygeal level. One tail was first used to obtain CT images and then was used to make anatomical sections. The second tail was dissected to individualize the ligaments and the muscular planes, then the tail was completely stripped to bone in order to obtain the coccygeal bones to make a water immersion ultrasound study. Phase 2: Fifteen standardbreed female horses, undergoing perineal surgical procedures, were enrolled in the study. After individuation of anatomical landmarks done in phase 1, images of the sacro-coccygeal zone were first collected from the horses always by the same operator in order to acquire the technique. Than each horse was sedated with xylazine 0.5 mg/kg IV and the registration of data started; one expert operator and different inexpert operators individuated the needle insertion point for the epidural space with the classical method described by Skarda et al., 2009. The insertion point was marked with a specific dot for inexpert and expert operators. Then ultrasound images of the coccygeal (Co) spaces were taken and the most appropriate insertion point was detected. The distance between the expert and the inexpert points, the expert and the ultrasound technique points and between the inexpert and the ultrasound technique points were measured with a caliber. After the measurements were acquired, a surgical scrub of the area was done and an epidural needle insertion was performed at the ultrasound individuated point. The depth of the epidural space was individuated by ultrasound. The Thouy needle was then inserted with a 90° angle respect to the skin and the right positioning of the tip needle was confirmed by the hanging drop technique. Stage 1: CT and ultrasound images of the tails confirmed that the spinous processes of coccygeal vertebrae are incomplete. Specific ultrasound images can be individuated and the depth of the epidural space can be measured. Stage 2: mean depths of epidural space recorded at the spaces between Co1 and Co2 and between Co2 and Co3 were 3.069 ± 0.36 and 2.63 ± 0.29 respectively. Mean distance between the expert and inexpert points was 1.18 ± 0.94 cm, between the inexpert and ultrasound points was 2.16 ± 1.77 cm and between the expert and ultrasound points was 1.26 ± 1.46 cm. The hanging drop technique confirmed the right positioning of the needle in all horses. Ultrasound evaluation of the epidural space at coccygeal level is feasible and quite easy. This study puts in evidence that the ultrasound technique can be more accurate than both inexpert and expert operators in individuating the epidural injection point. This technique can also be used to know the depth of the epidural space. The technique may be a support tool and not a guide because the 90° angle of the needle does not allow the direct visualisation under the ultrasound probe during the procedure. Further studies are to be performed to evaluate the possibility to make the procedure under the ultrasound direct visualization. Skarda RT, Muir WW, Hubbel JAE, Local Anesthetic Drugs and Technique in Muir WW, Hubbel JAE “Equine Anesthesia Monitoring and Emergency Therapy Second Edition, St Louis, Saunders Elsevier, 2009. Anaesthesiology and pain therapy epidural anesthesia, horse, ultrasoun