Total intravenous anaesthesia in dogs: development of a target controlled infusion (TCI) scheme for propofol

The aim of this work was to develop a propofol (PPF) based Total Intravenous Anaesthesia (TIVA) technique to be used in dogs by veterinary surgeons in practice. As PPF is a poor analgesic agent, this work also looked into the development of a co-infusion scheme for the potent alpha2-adrenoceptor agonist medetomidine (MED) and its active enantiomer dexmedetomidine (DEX). The study was divided into 4 phases. In phase one, canine PPF pharmacokinetic (PK) parameters, derived from previous studies reported in the literature, were incorporated to a Target Controlled Infusion (TCI) system. This approach, comprising computer software incorporated into a syringe driver, which will deliver PPF to a predicted blood concentration, is widely used in humans. The performance of the system was investigated in 6 greyhounds and 10 mixed-breed dogs undergoing routine dental work by comparing predicted with measured PPF concentrations in venous blood samples obtained during and following TCI PPF anaesthesia. The optimal induction target was 3 mgml-1, and an adequate depth and a satisfactory quality of anaesthesia were achieved with mean maintenance targets of between 3.4 and 4.5 mgml-1 of PPF. The performance of the TCI system was considered clinically acceptable as the Median Prediction Error (MDPE%), a measure of bias, and the Median Absolute Performance Error (MADPE%), a measure of the accuracy, were -12.47 and 28.47 respectively, in the greyhounds and 1.56 and 24.79 respectively, in the mixed-breed dogs. The system was easy to use and the quality of anaesthesia was judged to be adequate for dental work. Phase 2 illustrated the inhibitory effect of MED and DEX on PPF metabolism at the level of the cytochrome P450 in rat and canine hepatic tissue and highlighted, therefore, the possible effect on the metabolism dependant performance of the TCI system. Before designing an infusion scheme for MED and studying its possible effect on PPF PK in vivo (phase 4), the purpose of phase 3 was to characterise cardiovascular and respiratory effects of MED administered IV to dogs anaesthetised with a TCI of PPF, and to assess its suitability for use in a TIVA regime. Eighty dogs, ASA 1 or 2, aged 0.5 to 8 years, were randomly allocated into 8 groups of 10 dogs according to the dose of MED administered (Groups 1-8: 0 (saline, 0.9%, 1 ml), 0.01, 0.03, 0.1, 0.3, 1, 3, 10 mcgkg-1 MED, respectively). Following premedication, anaesthesia was induced with a PPF target blood concentration of 3 mcgml-1 and maintained with a target concentration of 3.5 mcgml-1. Cardiovascular and respiratory parameters were recorded for 15 min post induction and before saline (group 1) or MED (groups 2-8) was injected slowly over 1 min. Medetomidine induced a dose-dependent reduction in heart rate (HR) and increase in systolic arterial blood pressure (ABP). At the time of maximum observed effect (2 min post MED injection), the ED50 for ABP and HR were 2.05 and 0.187 mcgkg-1 respectively, while the ED95 (doses of MED inducing 95% of the maximum effect) values were estimated to be 18.1 mcgkg-1 and 3.1 mcgkg-1, respectively. The no effect doses for MED were 0.01 mcgkg-1 for HR, and 0.1 mcgkg-1 for ABP. Minimal respiratory effects were observed in all groups except the group receiving 10 mcgkg-1 of MED where, by the end of the recording period (20 min post MED injection), 8 of 9 spontaneously breathing dogs became apnoeic after MED administration. Phase 4 was designed to develop and assess a stepped infusion scheme for MED and DEX in the TCI PPF anesthetised dog using MED PK parameters from O. Vainio (V1 = 470 mlkg-1, K12 = 0.0954, K21 = 0.0438, K10 = 0.0489); to observe the possible PK and PD (pharmacodynamic) interactions between PPF and the 2 alpha2-adrenoceptor agonists during co-infusion; to determine the minimum blood PPF infusion target (MIT) necessary to prevent purposeful movement during supramaximal noxious stimulation (tetanic twitch for 5 sec at the level of the 4th and 5th coccygeal vertebrae) with and without a co-infusion of MED or DEX and to confirm the DEX minimum analgesic blood concentration of 0.85 ngml-1. Six female beagle dogs, 7.3 (± 2.3) years old, were anaesthetised on 4 occasions, following a randomised cross over design: PPF TCI with either co-stepped infusion of saline (PS), MED (blood target of 1.7 ngml-1, PM), low DEX (blood target of 0.85 ngml-1, PLD) or high DEX (blood target of 1.7 ngml-1, PHD). The co-infusion was started 25 min after the start of anaesthesia (instrumentation period), while the MIT determination was conducted 15 min after the last step of the co-infusion. Venous blood samples were taken at specific times for determination of the PPF, MED and DEX plasma concentrations. The performance of the TCI system for PPF in the dog was only clinically acceptable in the PS and PLD treatments with MDPE% values of 18.85 and 25.94 respectively, and MDAPE% values of 18.85 and 35.80 respectively. In this study the use of DEX 0.85 ngml-1 had a similar PPF sparing effect to the equivalent MED blood concentration of 1.7 ngml-1, but with less effects on ABP, as well as on the performance of the TCI for PPF in the dog. Therefore, it could be concluded that DEX was more advantageous than MED given by infusion in PPF anaesthetised dogs. The study also confirmed the validity of the PK of MED from the previous study. The study redefined specific PK parameters for DEX, although the MED PK parameters could also be used. The study indicated that DEX blood concentrations as low as 0.85 ngml-1 decreased the measured PPF blood concentrations necessary to maintain anaesthesia during noxious stimulation by about 38%. However, although this study supported the suitability of the co-infusion of DEX during PPF anaesthesia in the dog, and the analgesic/sedative effects of DEX were present at the lowest blood concentrations with well maintained respiratory parameters, the CV effects were marked with a decrease in HR and CO and an increase in systolic and mean ABP. Further studies are therefore necessary to establish if a lower blood concentration of DEX will provide analgesia while preserving the CV system

Total intravenous anaesthesia in dogs : development of a target controlled infusion (TCI) scheme for propofol

The aim of this work was to develop a propofol (PPF) based Total Intravenous Anaesthesia (TIVA) technique to be used in dogs by veterinary surgeons in practice. As PPF is a poor analgesic agent, this work also looked into the development of a co-infusion scheme for the potent alpha2-adrenoceptor agonist medetomidine (MED) and its active enantiomer dexmedetomidine (DEX). The study was divided into 4 phases. In phase one, canine PPF pharmacokinetic (PK) parameters, derived from previous studies reported in the literature, were incorporated to a Target Controlled Infusion (TCI) system. This approach, comprising computer software incorporated into a syringe driver, which will deliver PPF to a predicted blood concentration, is widely used in humans. The performance of the system was investigated in 6 greyhounds and 10 mixed-breed dogs undergoing routine dental work by comparing predicted with measured PPF concentrations in venous blood samples obtained during and following TCI PPF anaesthesia. The optimal induction target was 3 mgml-1, and an adequate depth and a satisfactory quality of anaesthesia were achieved with mean maintenance targets of between 3.4 and 4.5 mgml-1 of PPF. The performance of the TCI system was considered clinically acceptable as the Median Prediction Error (MDPE%), a measure of bias, and the Median Absolute Performance Error (MADPE%), a measure of the accuracy, were -12.47 and 28.47 respectively, in the greyhounds and 1.56 and 24.79 respectively, in the mixed-breed dogs. The system was easy to use and the quality of anaesthesia was judged to be adequate for dental work. Phase 2 illustrated the inhibitory effect of MED and DEX on PPF metabolism at the level of the cytochrome P450 in rat and canine hepatic tissue and highlighted, therefore, the possible effect on the metabolism dependant performance of the TCI system. Before designing an infusion scheme for MED and studying its possible effect on PPF PK in vivo (phase 4), the purpose of phase 3 was to characterise cardiovascular and respiratory effects of MED administered IV to dogs anaesthetised with a TCI of PPF, and to assess its suitability for use in a TIVA regime. Eighty dogs, ASA 1 or 2, aged 0.5 to 8 years, were randomly allocated into 8 groups of 10 dogs according to the dose of MED administered (Groups 1-8: 0 (saline, 0.9%, 1 ml), 0.01, 0.03, 0.1, 0.3, 1, 3, 10 mcgkg-1 MED, respectively). Following premedication, anaesthesia was induced with a PPF target blood concentration of 3 mcgml-1 and maintained with a target concentration of 3.5 mcgml-1. Cardiovascular and respiratory parameters were recorded for 15 min post induction and before saline (group 1) or MED (groups 2-8) was injected slowly over 1 min. Medetomidine induced a dose-dependent reduction in heart rate (HR) and increase in systolic arterial blood pressure (ABP). At the time of maximum observed effect (2 min post MED injection), the ED50 for ABP and HR were 2.05 and 0.187 mcgkg-1 respectively, while the ED95 (doses of MED inducing 95% of the maximum effect) values were estimated to be 18.1 mcgkg-1 and 3.1 mcgkg-1, respectively. The no effect doses for MED were 0.01 mcgkg-1 for HR, and 0.1 mcgkg-1 for ABP. Minimal respiratory effects were observed in all groups except the group receiving 10 mcgkg-1 of MED where, by the end of the recording period (20 min post MED injection), 8 of 9 spontaneously breathing dogs became apnoeic after MED administration. Phase 4 was designed to develop and assess a stepped infusion scheme for MED and DEX in the TCI PPF anesthetised dog using MED PK parameters from O. Vainio (V1 = 470 mlkg-1, K12 = 0.0954, K21 = 0.0438, K10 = 0.0489); to observe the possible PK and PD (pharmacodynamic) interactions between PPF and the 2 alpha2-adrenoceptor agonists during co-infusion; to determine the minimum blood PPF infusion target (MIT) necessary to prevent purposeful movement during supramaximal noxious stimulation (tetanic twitch for 5 sec at the level of the 4th and 5th coccygeal vertebrae) with and without a co-infusion of MED or DEX and to confirm the DEX minimum analgesic blood concentration of 0.85 ngml-1. Six female beagle dogs, 7.3 (± 2.3) years old, were anaesthetised on 4 occasions, following a randomised cross over design: PPF TCI with either co-stepped infusion of saline (PS), MED (blood target of 1.7 ngml-1, PM), low DEX (blood target of 0.85 ngml-1, PLD) or high DEX (blood target of 1.7 ngml-1, PHD). The co-infusion was started 25 min after the start of anaesthesia (instrumentation period), while the MIT determination was conducted 15 min after the last step of the co-infusion. Venous blood samples were taken at specific times for determination of the PPF, MED and DEX plasma concentrations. The performance of the TCI system for PPF in the dog was only clinically acceptable in the PS and PLD treatments with MDPE% values of 18.85 and 25.94 respectively, and MDAPE% values of 18.85 and 35.80 respectively. In this study the use of DEX 0.85 ngml-1 had a similar PPF sparing effect to the equivalent MED blood concentration of 1.7 ngml-1, but with less effects on ABP, as well as on the performance of the TCI for PPF in the dog. Therefore, it could be concluded that DEX was more advantageous than MED given by infusion in PPF anaesthetised dogs. The study also confirmed the validity of the PK of MED from the previous study. The study redefined specific PK parameters for DEX, although the MED PK parameters could also be used. The study indicated that DEX blood concentrations as low as 0.85 ngml-1 decreased the measured PPF blood concentrations necessary to maintain anaesthesia during noxious stimulation by about 38%. However, although this study supported the suitability of the co-infusion of DEX during PPF anaesthesia in the dog, and the analgesic/sedative effects of DEX were present at the lowest blood concentrations with well maintained respiratory parameters, the CV effects were marked with a decrease in HR and CO and an increase in systolic and mean ABP. Further studies are therefore necessary to establish if a lower blood concentration of DEX will provide analgesia while preserving the CV system.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A review of the pharmacology and clinical application of alfaxalone in cats

AbstractAlfaxalone-2-hydroxpropyl-β-cyclodextrin (alfaxalone-HPCD) was first marketed for veterinary use in Australia in 2001 and has since progressively became available throughout the world, including the USA, where in 2012 Food and Drug Administration (FDA) registration was granted. Despite the growing body of published works and increasing global availability of alfaxalone-HPCD, the accumulating evidence for its use in cats has not been thoroughly reviewed. The purpose of this review is: (1) to detail the pharmacokinetic properties of alfaxalone-HPCD in cats; (2) to assess the pharmacodynamic properties of alfaxalone-HPCD, including its cardiovascular, respiratory, central nervous system, neuromuscular, hepatic, renal, haematological, blood-biochemical, analgesic and endocrine effects; and (3) to consider the clinical application of alfaxalone-HPCD for sedation, induction and maintenance of anaesthesia in cats. Based on the published literature, alfaxalone-HPCD provides a good alternative to the existing intravenous anaesthetic options for healthy cats

Intravenous acetaminophen does not provide adequate postoperative analgesia in dogs following ovariohysterectomy

(1) Objective: To investigate the analgesic effects of intravenous acetaminophen after intravenous administration in dogs presenting for ovariohysterectomy. (2) Methods: 14 ASA I client-owned female entire dogs. In this randomized, blinded, clinical study, dogs were given meperidine and acepromazine intramuscularly before induction of anesthesia with intravenous propofol. Anesthesia was maintained with isoflurane in oxygen. Intravenous acetaminophen 20 mg/kg or 0.9% NaCl was administered postoperatively. Pain assessments were conducted using the Glasgow Pain Scale short form before premedication and at 10, 20, 60, 120, and 180 min post-extubation or until rescue analgesia was given. The pain scores, times, and incidences of rescue analgesia between the groups was compared. Blood was collected before and 2, 5, 10, 20, 40, and 80 min after acetaminophen administration. Acetaminophen plasma concentration was quantified by liquid chromatography-mass spectrometry. The acetaminophen plasma concentration at the time of each pain score evaluation was subsequently calculated. (3) Results: There was no significant difference in pain scores at 10 min, highest pain scores, or time of rescue analgesia between groups. In each group, 3 dogs (43%) received rescue analgesia within 20 min. (4) Conclusions: Following ovariohysterectomy in dogs, there was no detectable analgesic effect of a 20 mg/kg dosage of intravenous acetaminophen administered at the end of surgery

PERAN SERTA MAHASISWA KKN-T DALAM PEMBANGUNAN MASYARAKAT/ PEMBERDAYAAN MASYARAKAT DI DESA RUBUNG BUYUNG, KECAMATAN CEMPAGA, KABUPATEN KOTAWARINGIN TIMUR, KALIMANTAN TENGAH

Kuliah kerja nyata merupakan bentuk penerapan ilmu pengetahuan serta pengabdian mahasiswa dengan terjun langsung dan ikut serta dalam proses pembangunan di lingkungan masyarakat. Sebagai wujud pelaksanaan tri dharma perguruan tinggi, kuliah kerja nyata ini didasarkan pada aspek keilmuan dan implementasinya yang dilakukan dalam proses mengenali, menganalisis potensi, serta memecahkan persoalan dilingkungan masyarakat. Tujuan pelaksanaan kuliah kerja nyata ialah untuk menumbuhkan kesadaran serta kemampuan masyarakat akan potensi individu serta sumber daya yang dimiliki agar dapat berpartisipasi aktif dalam pembangunan secara mandiri. Metode pelaksanaan program kuliah kerja nyata dilakukan dengan terjun langsung dalam lingkungan masyarakat dengan keterlibatan masyarakat desa dan mahasiswa sesuai tugas pokok, fungsi dan kompetensi yang dimiliki. Melalui pelaksanaan kuliah kerja nyata ini diperoleh hasil yakni terbentuknya masyarakat yang berkembang pada aspek pola pikir dan perilaku serta kesadaran masyarakat untuk aktif mengembangkan potensi dan mengelola sumber daya sumber daya alam secara terarah dan bernilai positif. Dari hasil yang didapatkan, masyarakat dari yang pasif menjadi lebih peka terhadap kelestarian lingkungan serta mampu mengembangkan potensi pengelolaan sumber daya air bersih demi meningkatkan kualitas kehidupan masyarakat. Hasil dari kegiatan ini akan mengembangkan wawasan masyarakat untuk berinovasi agar nantinya masyarakat bisa mandiri sehingga kegiatan desa akan berjalan dengan efekti

Reducing the prosthesis modulus by inclusion of an open space lattice improves osteogenic response in a sheep model of extraarticular defect

Introduction: Stress shielding is a common complication following endoprosthetic reconstruction surgery. The resulting periprosthetic osteopenia often manifests as catastrophic fractures and can significantly limit future treatment options. It has been long known that bone plates with lower elastic moduli are key to reducing the risk of stress shielding in orthopedics. Inclusion of open space lattices in metal endoprostheses is believed to reduce the prosthesis modulus potentially improving stress shielding. However, no in vivo data is currently available to support this assumption in long bone reconstruction. This manuscript aims to address this hypothesis using a sheep model of extraarticular bone defect.Methods: Initially, CT was used to create a virtual resection plan of the distal femoral metaphyses and to custom design endoprostheses specific to each femur. The endoprostheses comprised additively manufactured Ti6Al4V-ELI modules that either had a solid core with a modulus of ∼120 GPa (solid implant group) or an open space lattice core with unit cells that had a modulus of 3–6 GPa (lattice implant group). Osteotomies were performed using computer-assisted navigation followed by implantations. The periprosthetic, interfacial and interstitial regions of interest were evaluated by a combination of micro-CT, back-scattered scanning electron microscopy (BSEM), as well as epifluorescence and brightfield microscopy.Results: In the periprosthetic region, mean pixel intensity (a proxy for tissue mineral density in BSEM) in the caudal cortex was found to be higher in the lattice implant group. This was complemented by BSEM derived porosity being lower in the lattice implant group in both caudal and cranial cortices. In the interfacial and interstitial regions, most pronounced differences were observed in the axial interfacial perimeter where the solid implant group had greater bone coverage. In contrast, the lattice group had a greater coverage in the cranial interfacial region.Conclusion: Our findings suggest that reducing the prosthesis modulus by inclusion of an open-space lattice in its design has a positive effect on bone material and morphological parameters particularly within the periprosthetic regions. Improved mechanics appears to also have a measurable effect on the interfacial osteogenic response and osteointegration