Intraperitoneal and incisional ropivacaine did not improve postoperative analgesia after multimodal anaesthesia compared with saline in dogs undergoing ovariohysterectomy.

INTRODUCTION: Intraperitoneal administration of local anaesthetics may reduce postoperative pain after ovariohysterectomy in dogs. The aim of this prospective, randomised, blinded, placebo-controlled clinical trial was to compare postoperative analgesia and opioid requirements after intraperitoneal and incisional administration of ropivacaine versus 0,9 % NaCl (saline). Forty-three client-owned dogs were enrolled in the study and anaesthetised using a standardized protocol that included premedication with acepromazine (0,03-0,05 mg/kg) and dexmedetomidine (0,01 mg/kg) intramuscularly. Anaesthesia was induced with propofol titrated to effect and ketamine (1 mg/kg) intravenously and maintained with isoflurane in oxygen. The analgesic regimen included carprofen (4 mg/kg) subcutaneously and morphine (0,2 mg/kg) intravenously. Depending on group assignment, each dog received either an intraperitoneal and incisional splash with ropivacaine (2 mg/kg and 1 mg/kg, respectively) (group R), or an equal volume of saline (group S). Buprenorphine (0,02 mg/kg) was administered intramuscularly once the uterus was removed. Sedation and pain were assessed 0,5, 1, 2, 4, 6 and 8 hours after extubation using a sedation scale, the short form of the Glasgow Composite Pain Scale (CMPS-SF) and a dynamic interactive visual analogue scale (DIVAS). Postoperatively, buprenorphine (0,01 mg/kg) was administered intravenously if dogs scored 6/24 on CMPS-SF. The ordinal mixed model showed no difference in pain scores between groups. Fisher's exact test showed no significant difference in postoperative buprenorphine requirements between group S (3/22 dogs) and group R (1/21 dogs) at the doses used. In addition, lower sedation scores were associated with higher DIVAS scores. In this multimodal analgesic protocol, ropivacaine could not improve analgesia compared to saline.

INTRODUCTION: L'administration intrapéritonéale d'anesthésiques locaux peut réduire la douleur postopératoire après une ovariohystérectomie chez la chienne. L'objectif de cet essai clinique prospectif, randomisé, en aveugle et contrôlé par placebo était de comparer l'analgésie postopératoire et les besoins en opioïdes après l'administration intrapéritonéale et incisionnelle de ropivacaïne par rapport à du NaCl 0,9 % (sérum physiologique). Quarante-trois chiennes appartenant à des clients ont été enrôlés dans l'étude et anesthésiés selon un protocole standardisé comprenant une prémédication par acépromazine (0,03 - 0,05 mg/kg) et dexmedetomidine (0,01 mg/kg) par voie intramusculaire. L'anesthésie a été induite avec du propofol dosé à l'effet et de la kétamine (1 mg/kg) par voie intraveineuse et maintenue avec de l'isoflurane dans de l'oxygène. Le traitement analgésique comprenait du carprofène (4 mg/kg) par voie sous-cutanée et de la morphine (0,2 mg/kg) par voie intraveineuse. En fonction de son affectation à un groupe, chaque chien a reçu soit une injection intrapéritonéale et incisionnelle de ropivacaïne (2 mg/kg et 1 mg/kg, respectivement) (groupe R), soit un volume égal de solution saline (groupe S). La buprénorphine (0,02 mg/kg) a été administrée par voie intramusculaire après l'ablation de l'utérus. La sédation et la douleur ont été évaluées 0,5, 1, 2, 4, 6 et 8 heures après l'extubation à l'aide d'une échelle de sédation, de la forme courte de l'échelle composite de douleur de Glasgow (CMPS-SF) et d'une échelle visuelle analogique interactive dynamique (DIVAS). En postopératoire, de la buprénorphine (0,01 mg/kg) a été administrée par voie intraveineuse si les chiens obtenaient un score de 6/24 sur l'échelle CMPS-SF. Le modèle mixte ordinal n'a montré aucune différence dans les scores de douleur entre les groupes. Le test exact de Fisher n'a pas montré de différence significative dans les besoins postopératoires en buprénorphine entre le groupe S (3/22 chiens) et le groupe R (1/21 chiens) aux doses utilisées. De plus, des scores de sédation plus faibles étaient associés à des scores DIVAS plus élevés. Dans ce protocole d'analgésie multimodale, la ropivacaïne n'a pas permis d'améliorer l'analgésie par rapport au sérum physiologique.

Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin.

Sepsis of Gram negative bacterial origin results in lipopolysaccharide-induced endotoxemia. This often leads to acute kidney injury (AKI) and its recognition remains a challenge and delays treatment. As renal damage occurs before a rise in serum creatinine is detected, new early biomarkers of kidney injury need to be explored. The aim of this study was to determine changes in serum parameters of renal function and urine biomarkers of renal injury. This was a descriptive study. Endotoxemia was induced intravenously in six anaesthetized Beagles (T1). To achieve normotension, dogs received fluids (T2), followed by a continuous infusion of noradrenaline and dexmedetomidine or 0.9% NaCl (T3). Ten minutes later, the dogs received fluids (T4) and noradrenaline and dexmedetomidine or 0.9% NaCl in a crossover manner (T5). At each timepoint, blood and urine were collected for serum creatinine, urea, symmetric dimethylarginine, urine protein/creatinine (UPC) ratio, urine neutrophil-gelatinase-associated lipocalin (U-NGAL), U-NGAL/creatinine ratio, urine clusterin (U-clusterin) and U-clusterin/creatinine ratio. Data were analyzed using a mixed-effect model taking into account time and stage of veterinary AKI (VAKI). Three of six dogs had a VAKI stage ≥1; one with anuria and elevated creatinine. Serum creatinine (P < 0.001), U-NGAL/creatinine ratio (P = 0.01) and U-clusterin/creatinine ratio increased over time (P < 0.01). The UPC ratio (mean (range) 0.68 (0.35-2.3) versus 0.39 (0.15-0.71) P < 0.01) and U-NGAL (3164 pg/mL (100-147,555) versus 100 (100-14,524), P = 0.01) were higher in VAKI stage ≥1 versus stage 0, respectively. Endotoxemia induced VAKI stage ≥1 in half of the dogs. Repeated measurement of selected parameters could detect AKI early.

Effect of early administration of tranexamic acid on ongoing haemorrhage in dogs with non-surgically treated haemoabdomen.

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic drug used for the prophylaxis and treatment of haemorrhage of various origin. This retrospective study investigated the effect of TXA on ongoing bleeding in dogs with nonsurgically treated haemoabdomen. The study population consisted of 48 dogs treated in the period 2009-2020 at the Small Animal Clinic of the Vetsuisse Faculty of Zurich. Twenty-eight of 48 dogs were treated with 20 mg/kg TXA IV within 3h of diagnosis of haemoabdomen. Dogs treated with and without TXA were monitored over 48 hours for signs of ongoing haemorrhage. Ongoing haemorrhage was defined as an increase in abdominal fluid accumulation, a decrease in haematocrit of >5% over time or need for surgical exploration after at least 12 hours of medical treatment. Transfusion requirements, cumulative amount of fluid therapy, heart rate, respiratory rate, temperature, systolic and mean arterial pressure, estimate of abdominal fluid identified by FAST analysis, venous haematocrit, abdominal haematocrit, serum albumin, serum lactate and thrombocyte count were extracted from patient records at 6, 12, 24 and 48 hours after diagnosis of haemoabdomen. Groups were comparable at presentation, however dogs of the TXA group showed a significantly lower abdominal haematocrit at presentation (37 vs 45%, P=0,034) and a higher fluid accumulation (P=0,019), both persisting over time. None of the outcome parameters for ongoing haemorrhage was significantly different between groups. Transfusion requirement was low and similar in both groups. Of interest, none of the 16 dogs undergoing thromboelastometry showed hyperfibrinolysis at presentation. We conclude that other mechanisms than antifibrinolytic therapy was responsible for cessation of bleeding in the majority of patients.

INTRODUCTION: L'acide tranexamique (TXA) est un médicament anti fibrinolytique utilisé pour la prophylaxie et le traitement des hémorragies d'origines diverses. Cette étude rétrospective a examiné l'effet du TXA sur les saignements en cours chez les chiens présentant un hémoabdomen traité sans chirurgie. La population étudiée était composée de 48 chiens traités entre 2009 et 2020 à la clinique pour petits animaux de la faculté Vetsuisse de Zurich. Vingt-huit des 48 chiens ont été traités avec 20 mg/kg de TXA IV dans les 3 heures suivant le diagnostic de l'hémoabdomen. Les chiens traités avec et sans TXA ont été surveillés pendant 48 heures pour détecter les signes d'hémorragie en cours. L'hémorragie en cours a été définie comme une augmentation de l'accumulation de liquide abdominal, une diminution de l'hématocrite de >5% dans le temps ou la nécessité d'une exploration chirurgicale après au moins 12 heures de traitement médical. Les besoins transfusionnels, la quantité cumulative de traitement liquidien, la fréquence cardiaque, la fréquence respiratoire, la température, la pression artérielle systolique et moyenne, l'estimation du liquide abdominal identifié par l'analyse FAST, l'hématocrite veineux, l'hématocrite abdominal, l'albumine sérique, le lactate sérique et la numération des thrombocytes ont été extraits des dossiers des patients à 6, 12, 24 et 48 heures après le diagnostic d'hémoabdomen. Les groupes étaient comparables à la présentation, mais les chiens du groupe TXA présentaient un hématocrite abdominal significativement plus faible à la présentation (37 vs 45 %, P=0,034) et une accumulation de liquide plus importante (P=0,019), ces deux phénomènes persistant dans le temps. Aucun des paramètres de résultat pour l'hémorragie en cours n'était significativement différent entre les groupes. Les besoins en transfusion étaient faibles et similaires dans les deux groupes. Il est intéressant de noter qu'aucun des 16 chiens soumis à la thromboélastométrie ne montrait d'hyperfibrinolyse à la présentation. Nous concluons que d'autres mécanismes que le traitement anti fibrinolytique étaient responsables de l'arrêt des saignements chez la majorité des patients.

Characteristics of hyperfibrinolysis in dogs and cats demonstrated by rotational thromboelastometry (ROTEM).

Hyperfibrinolysis (HFL) is a pathophysiological mechanism that has not been described in dogs or cats extensively. The aim of this study was to describe rotational thromboelastometry (ROTEM) parameters and underlying diagnosis in dogs and cats with HFL and evaluate association with bleeding diathesis. The ROTEM database was retrospectively searched for EXTEM (ROTEM activated with proprietary tissue factor) tracings with maximum lysis at 60min ≥15%. Concurrent ROTEM and plasma coagulation tests, thrombocyte number, diagnosis and survival to hospital discharge were extracted from medical records. Analysis of differences between dogs and cats and of factors associated with bleeding, fulminant HFL (clot breakdown within 30min) and survival to hospital discharge were performed. Hyperfibrinolysis was detected in eight cats presenting with haemoabdomen or haemothorax (n=4/8, 50%) and trauma (n=3/8, 38%) and in 36 dogs with angiostrongylosis (n=12, 33%), neoplasia (n=7, 19%), liver disease (n=4, 11%) and others including apparently healthy dogs (n=3, 8%). Hyperfibrinolysis was associated with prolonged EXTEM and APTEM (EXTEM with added apoprotein for inhibition of HFL) clotting time and decreased FIBTEM (EXTEM with added cytochalasin D for inhibition of thrombocytes) maximum clot firmness (MCF) in dogs and cats and with decreased EXTEM MCF in dogs. Bleeding dogs had significantly hypocoagulable EXTEM tracings. Fulminant HFL was associated with severe hypofibrinogenaemia in dogs (P=0.005) and was not associated with survival to hospital discharge. Evidence of HFL was demonstrated in dogs and cats with bleeding, trauma, parasitic and neoplastic disease. HFL is associated with late and weak clot formation.

Hyperfibrinolysis and Hypofibrinogenemia Diagnosed With Rotational Thromboelastometry in Dogs Naturally Infected With Angiostrongylus vasorum.

BACKGROUND: The pathomechanism of Angiostrongylus vasorum infection-associated bleeding diathesis in dogs is not fully understood. OBJECTIVE: To describe rotational thromboelastometry (ROTEM) parameters in dogs naturally infected with A. vasorum and to compare ROTEM parameters between infected dogs with and without clinical signs of bleeding. ANIMALS: A total of 21 dogs presented between 2013 and 2016. METHODS: Dogs with A. vasorum infection and ROTEM evaluation were retrospectively identified. Thrombocyte counts, ROTEM parameters, clinical signs of bleeding, therapy, and survival to discharge were retrospectively retrieved from patient records and compared between dogs with and without clinical signs of bleeding. RESULTS: Evaluation by ROTEM showed hyperfibrinolysis in 8 of 12 (67%; 95% CI, 40-86%) dogs with and 1 of 9 (11%; 95% CI, 2-44%) dogs without clinical signs of bleeding (P = .016). Hyperfibrinolysis was associated with severe hypofibrinogenemia in 6 of 10 (60%; 95% CI, 31-83%) of the cases. Hyperfibrinolysis decreased or resolved after treatment with 10-80 mg/kg tranexamic acid. Fresh frozen plasma (range, 14-60 mL/kg) normalized follow-up fibrinogen function ROTEM (FIBTEM) maximal clot firmness in 6 of 8 dogs (75%; 95% CI, 41-93%). Survival to discharge was 67% (14/21 dogs; 95% CI, 46-83%) and was not different between dogs with and without clinical signs of bleeding (P = .379). CONCLUSION AND CLINICAL IMPORTANCE: Hyperfibrinolysis and hypofibrinogenemia were identified as an important pathomechanism in angiostrongylosis-associated bleeding in dogs. Hyperfibrinolysis and hypofibrinogenemia were normalized by treatment with tranexamic acid and plasma transfusions, respectively.

Femoral and sciatic nerve blockades and incision site infiltration in rabbits undergoing stifle joint arthrotomy.

This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and received morphine intramuscularly. The sciatic and femoral nerves of the leg to be operated on were located using a nerve stimulator (1 Hz, 0.5 mA). Rabbits were assigned to a treatment group (LB; n = 12) or a placebo group (P; n = 12) in a randomized blinded fashion. Group LB received lidocaine 2% (1 mg/kg) combined with bupivacaine 0.5% (0.25 mg/kg) injections around the sciatic and femoral nerves (0.1 mL/kg total volume per site) and subcutaneous infiltration of the incision site with lidocaine 1% (1.25 mg/kg). Group P received the same volume of 0.9% NaCl. Rabbits in group P required higher doses of intraoperative fentanyl and propofol to reduce heart rate and suppress increase in systolic blood pressure, and maintain an adequate anaesthetic plane. Interventional analgesia (buprenorphine and carprofen) was required significantly earlier in rabbits in group P (2 and 6 h after the first nerve blockade, respectively) based on assessment of their pain-related behaviour and range of motion. Using a visual analogue scale (0 mm= no pain to 100 mm= maximal possible pain), rabbits in group LB were judged to show significantly less pain compared with rabbits in group P (14 ± 10 mm and 37 ± 25 mm, respectively) 2 h after nerve blockade. In conclusion, this technique of perineural analgesia combined with incision site infiltration reduced intraoperative fentanyl requirements and improved postoperative analgesia in rabbits.

[Bupivacaine toxicity and propofol anesthesia : animal study on intravascular bupivacaine injection]. / Bupivacaintoxizität und Propofolanästhesie : Tierstudie zur intravasalen Bupivacaininjektion.

BACKGROUND: Several reports have confirmed the efficacy of Intralipid® (containing soya bean oil, egg phospholipids, glycerin and water) in the therapy of systemic local anesthetic intoxication. Pretreatment with Intralipid® shifted the dose-response to bupivacaine-induced asystole in rats. Whether intravenous anesthesia with propofol in the widely used medium chain triglyceride lipid emulsion increases the therapeutic range of systemically administered bupivacaine or not is unknown and was investigated in this study. METHODS: A total of 30 piglets aged 2-6 weeks and weighing 4.5-6.5 kg were randomized into 2 groups and anesthetized with sevoflurane (group S) alone or with propofol 10 mg/kg body weight (BW)/h plus sevoflurane (group PS). After 60 min of steady state anesthesia arterial blood was sampled for assessment of blood gases, acid-base state and triglyceride plasma concentrations. Thereafter bupivacaine 0.125% was continuously infused by an infusion syringe pump through a central venous line at a rate of 4 mg/kg BW/min until invasively measured mean arterial pressure (MAP) was reduced by 50% of initial value. The bupivacaine infusion was stopped, blood for assessment of bupivacaine plasma concentration was drawn and the spontaneous hemodynamic course was observed. Resuscitation was not attempted. Results are presented as median and range. The Mann-Whitney U-test was used to assess differences between the two groups for triglyceride as well as for bupivacaine plasma concentrations measured at MAP 50%. A p-value≤0.05 was considered to be significant. RESULTS: Baseline conditions (arterial blood pH, plasma protein and triglyceride plasma concentrations) did not differ significantly between the two groups. After 1 h of anesthesia, triglyceride plasma concentrations were significantly increased in group PS (median 0.69 mmol/l) compared to the corresponding baseline values (median 0.14 mmol/l; p<0.001) and to the 1 h values of group S (median 0.16 mmol/l; p<0.001). The total amount of bupivacaine administered was 9 mg/kg BW in both groups (6-13 mg/kg BW in group S, 5-13 mg/kg BW in group PS). Resulting bupivacaine plasma concentrations were 180 µmol/l (83-686 µmol/l) in group S and 185 µmol/l (130-465 µmol/l) in group PS. However, the total amount of bupivacaine administered and bupivacaine plasma concentrations at MAP 50% did not reveal statistically significant differences between the two groups but a huge variability of both parameters within each group was observed. None of the 30 piglets spontaneously recovered and they died from pulseless electrical activity or from asystolic cardiac arrest. The time from MAP 50% until cardiac arrest demonstrated a large variability but did not reveal significant differences between the two groups. The time to cardiac arrest was similar in both groups. CONCLUSION: Medium/long chain triglyceride lipid emulsion (50:50) as widely used in propofol solutions did not increase therapeutic safety in cases of intravascular bupivacaine administration in this piglet model.

Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs.

BACKGROUND: It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. METHODS: Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg(-1) bupivacaine infused. RESULTS: Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93% and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg(-1) infused. CONCLUSIONS: Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administered.

Electrocardiographic alterations during intravascular application of three different test doses of bupivacaine and epinephrine: experimental study in neonatal pigs.

BACKGROUND: Origin of electrocardiographic (ECG) alterations during intravascular injection of local anaesthetic solutions is controversial. The aim of this study was to elucidate whether epinephrine, bupivacaine or their combination is responsible for ECG alteration. METHODS: Forty-five piglets were randomized into three groups. After induction of general anaesthesia using sevoflurane and peripheral venous cannulation, the trachea was intubated, the lungs were artificially ventilated, and anaesthesia was maintained by sevoflurane. Under steady state 0.2 ml kg(-1) and after 10 min 0.4 ml kg(-1) of one of the following three test solutions was administered i.v.: bupivacaine 0.125% (Group 1), bupivacaine 0.125%+epinephrine 1:200 000 (Group 2), and plain epinephrine 1:200,000 (Group 3). The ECG was analysed for alterations in heart rate and T-elevation. RESULTS: After injection of 0.2 or 0.4 ml kg(-1) test solution, an increase in heart rate of at least 10% was found in none of Group 1 and in all of Groups 2 and 3. After application of 0.2 ml kg(-1) test solution, T-elevation was found in 7% of Group 1 and in 93% of Groups 2 and 3. The injection of 0.4 ml kg(-1) revealed a T-elevation in 27%, 100%, and 100%, respectively, in Groups 1, 2, and 3. CONCLUSIONS: This animal model demonstrated that increases in heart rate and T-elevation in the ECG during i.v. application of a common test dose (0.2 ml kg(-1)) of bupivacaine are caused by epinephrine addition. Whether higher doses of bupivacaine alone can cause similar ECG changes or not requires further studies.

Respiratory and cardiovascular effects of doxapram and theophylline for the treatment of asphyxia in neonatal calves.

Respiratory stimulants are widely used in asphyxic neonatal calves despite a lack of data about their effectiveness and indications of possible side effects. The effect of doxapram and theophylline on respiratory, cardiovascular, and acid-base variables was investigated in 10 healthy neonatal calves (Bos Taurus). A venous, a peripheral arterial, and a pulmonary arterial catheter were placed, and central venous, pulmonary, and systemic blood pressures and cardiac output were measured using thermodilution technique. Doxapram, but not theophylline, led to an immediate increase in respiratory rate (P

Cardiopulmonary effects of dexmedetomidine in goats and sheep anaesthetised with sevoflurane.

In sheep, alpha(2)-agonists can induce severe hypoxaemia. In goats, reports on changes in oxygenation are inconsistent. The aim of this study was to compare the cardiopulmonary effects of dexmedetomidine in six goats and four sheep anaesthetised with sevoflurane and maintained at approximately 1 minimal alveolar concentration. The animals were ventilated mechanically and held in an upright position to minimise the influence of positioning on pulmonary function. After baseline cardiopulmonary measures, 2 microg/kg dexmedetomidine was injected intravenously over one minute, and measurements were made for 120 minutes. In both species, respiratory resistance, alveolar dead space and shunt fraction increased and thoracic compliance decreased significantly; arterial, pulmonary arterial, pulmonary capillary wedge and central venous pressures increased and heart rate and cardiac output decreased significantly. Arterial oxygen tension decreased significantly, with no significant difference between the goats and sheep. Wide interindividual differences were observed in both the goats (mean [sd] 144 [149.1] mmHg, range 54.8 to 443.7 mmHg) and sheep (mean [sd] 129.8 [132.1] mmHg, range 33.7 to 352.8 mmHg), but the cardiovascular and respiratory changes were similar in the two species.