Effect of desmopressin acetate administration on primary hemostasis in Doberman Pinschers with type-1 von Willebrand disease as assessed by a point-of-care instrument

OBJECTIVE: To evaluate primary hemostasis following administration of desmopressin acetate (DDAVP) to Doberman Pinschers with type-1 von Willebrand disease (vWD). ANIMALS: 16 nonanemic Doberman Pinschers with type-1 vWD. PROCEDURE: Closure time (CT), defined as time required for occlusion of an aperture by a platelet plug assessed within the point-of-care instrument, plasma von Willebrand factor (vWF) concentration, and buccal mucosal bleeding time (BMBT) were determined before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Baseline closure times measured with adenosine diphosphate ([ADP-CT], 108 to > 300 seconds; reference range, 52 to 86 seconds) and epinephrine ([EPI-CT], 285 to > 300 seconds; 97 to 225 seconds) as platelet agonists were prolonged in all dogs. Following DDAVP administration, ADP-CT (59 to 186 seconds) was significantly shortened from baseline, but there was no decrease in EPI-CT. Although mean plasma vWF concentration increased significantly after DDAVP administration, only 1 dog had an increase of > 35 U/dL. There was no correlation between increase in plasma vWF concentration and shortening of the ADP-CT. Baseline BMBT was prolonged in 12 of 14 dogs, with significant shortening of BMBT after DDAVP administration in 6 of 7 dogs. In vitro replacement of vWF-deficient plasma with plasma from an unaffected dog shortened the ADP-CT whereas in vitro addition of DDAVP had no effect. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of DDAVP to Doberman Pinschers with type-1 vWD resulted in improved hemostatic function, as assessed by the point-of-care instrument and shortening of BMBT, despite minimal increase in plasma vWF concentration.     

Effects of oxypolygelatin and dextran 70 on hemostatic variables in dogs

Objective To evaluate and compare coagulation variables following the administration of oxypolygelatin and dextran 70 to clinically healthy dogs. Study design Randomized cross‐over experimental study. Animals A total of eight healthy adult female Beagles aged 2–4 years old and weighing 11.8 ± 2.7 kg. Methods The dogs received a 15‐minute intravenous (IV) infusion of 5 mL kg^?1 oxypolygelatin or 10 mL kg^?1 6% dextran 70. Before (PRE) and at 2, 5, and 24 hours after administration, packed cell volume (PCV), total solids concentration (TS), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), platelet numbers (Plat), factor VIII coagulant activity (VIII:C), von Willebrand factor antigen concentration (vWf:Ag) and platelet function and buccal mucosal bleeding time (BMBT) were measured. Platelet function was assessed using aggregation and by measuring ATP release from aggregating platelets over 6 minutes, with 20, 10, and 5 µm ADP and 5 and 10 µg of collagen mL^?1 as platelet activation agonists. Results All baseline values were within our normal ranges, except for one dog that had low vWf:Ag PRE values prior to both dextran and oxypolygelatin administration. Following dextran and oxypolygelatin administration, the PCV and TP were significantly (p < 0.05) decreased. Plat, FIB, and vWf:Ag decreased, while BMBT and VIII:C increased following dextran administration. Dextran also caused a significant decrease in platelet aggregation in response to ADP. Oxypolygelatin caused a significant decrease in vWf:Ag, Plat, and FIB compared to PRE values. The total amount of ATP released, standardized to platelet number, did not vary significantly for either group at any sampling time from PRE values. No significant changes from PRE values were noted at any time in either group for PT or APTT. Conclusion At the doses administered, both dextran and oxypolygelatin can interfere with hemostatic variables in healthy dogs, but dextran's effect is more profound and prolonged when compared to oxypolygelatin. Clinical relevance Oxypolygelatin causes fewer hemostatic abnormalities when compared to dextran, making it a superior colloid for administration at the doses tested.     

The effects of lactated Ringer's solution (LRS) or LRS and 6% hetastarch on the colloid osmotic pressure, total protein and osmolality in healthy horses under general anesthesia

ObjectiveTo investigate changes in colloid osmotic pressure (COP), total protein (TP) and osmolality (OSM) during anesthesia in horses given intravenous lactated Ringer’s solution (LRS) or LRS and hetastarch (HES).Study designProspective, clinical trial.AnimalsFourteen horses presented for surgery. Mean age 8.3 ± 1.9 years; mean weight 452 ± 25 kg.MethodsHorses were premedicated with xylazine intravenously (IV); anesthesia was induced with ketamine and diazepam IV, and maintained with sevoflurane. Butorphanol was administered IV with pre-medications or immediately after induction. Xylazine was administered IV for recovery if necessary. LRS was administered IV to all horses with a target rate of 5–10 mL kg^?1 hour^?1. Half of the horses also received 6% HES, 2.5 mL kg^?1 over 1 hour in addition to LRS. Horses that received LRS only were considered the LRS group. Horses that received both LRS and HES were considered the LRS/HES group. Blood was drawn pre- and post-anesthesia, immediately following induction, and every 30 minutes throughout anesthesia. COP, TP and OSM were measured.ResultsCOP and TP significantly decreased at similar rates for both treatment groups from pre-anesthetic values. Pre-anesthetic COP was significantly greater in the LRS group when compared to the LRS/HES group pre-, post- and throughout anesthesia. In the LRS group post-anesthetic OSM was significantly different than the pre-anesthesia value and that for the LRS/HES group.Conclusions and clinical relevanceAdministration of IV HES (2.5 mL kg^?1, over 1 hour) in combination with LRS does not attenuate the decrease in COP typically seen during anesthesia with crystalloid administration alone. Based on these results, administration of HES at this rate and total volume would not be expected to prevent fluid shifts into the interstitium through its effects on COP.     

Effects of morphine and fentanyl constant rate infusion on urine output in healthy and traumatized dogs

ObjectiveTo determine whether healthy and traumatized dogs receiving a constant rate infusion (CRI) of either morphine or fentanyl have decreased urine production.Study designProspective randomized controlled study.Animal populationEighteen privately owned previously healthy dogs that had undergone trauma were included. Twenty-three privately owned healthy dogs were used as the controls.MethodsTraumatized dogs were randomized into one of two groups. Group Tmorphine received a CRI of morphine (0.12 mg kg⁻¹ hour⁻¹) and group Tfentanyl received a CRI of fentanyl (3 μg kg⁻¹ hour⁻¹) both administered in lactated Ringer’s solution (LRS) at a rate of 60 mL kg⁻¹ day⁻¹. Control healthy dogs were randomized into one of three groups. The LRS control group (CLRS) (n = 8) received LRS at a rate of 60 mL kg⁻¹ day⁻¹. Group Cmorphine (n = 8) and group Cfentanyl (n = 7) received the same infusions as Tmorphine and Tfentanyl, respectively. Collected data were identical for all groups and consisted of measuring total fluid administered, urine output, and urine specific gravity (USG) for a 24-hour period. An analysis of variance (anova) was used for statistical analysis and a p < 0.05 was considered statistically significant.ResultsUrine output was significantly decreased (p < 0.05) in all groups compared with the LRS control group. The end mean USG was significantly lower (p = 0.003) in the LRS control group compared with all other groups.ConclusionsThere was a decrease in urine output with a CRI of morphine or fentanyl in both healthy and traumatized dogs.Clinical relevanceDecreased urine output caused by an opioid effect might lead to improper assessments of renal function and urine production.     

Effects of DDAVP administrated subcutaneously in dogs with aspirin-induced platelet dysfunction and hemostatic impairment due to chronic liver diseases

To evaluate the hemostatic effects of desmopressin (DDAVP) in dogs with aspirin-induced platelet dysfunction and hemostatic impairment in chronic liver diseases, 3 microg/kg DDAVP was administrated subcutaneously. In aspirin-induced platelet dysfunction dogs (n=5), prolonged BMBT (buccal mucosal bleeding time) was shortened significantly after DDAVP injection (2.2 +/- 1.2 min, P<0.05). In dogs with chronic liver diseases (n=4), activated partial thromboplastin time (APTT) tended to shorten by 0.9 to 3.0 sec, and prolonged BMBT was shortened in two cases for 4.2 and 1.7 min after DDAVP injection. Therefore, the present results indicated that DDAVP shortened the prolonged BMBT in dogs with aspirin-induced platelet dysfunction and chronic liver disease. DDAVP might be helpful in hemostasis under invasive procedures such as biopsy or surgery for dogs with hemostatic impairment.     

Effects of carprofen, meloxicam and deracoxib on platelet function in dogs

ObjectiveTo determine effects of anti-inflammatory doses of COX-2 selective NSAIDs carprofen, meloxicam, and deracoxib on platelet function in dogs and urine 11-dehydro-thromboxane B2.Study designRandomized, blocked, crossover design with a 14-day washout period.AnimalsHealthy intact female Walker Hounds aged 1–6 years and weighing 20.5–24.2 kg.MethodsDogs were given NSAIDs for 7 days at recommended doses: carprofen (2.2 mg kg^?1, PO, every 12 hours), carprofen (4.4 mg kg^?1, PO, every 24 hours), meloxicam (0.2 mg kg^?1, PO, on the 1st day then 0.1 mg kg^?1, PO, every 24 hours), and deracoxib (2 mg kg^?1, PO, every 24 hours). Collagen/epinephrine and collagen/ADP PFA-100 cartridges were used to evaluate platelet function before and during and every other day after administration of each drug. Urine 11-dehydro-thromboxane B₂ was also measured before and during administration of each drug.ResultsAll NSAIDs significantly prolonged PFA-100 closure times when measured with collagen/epinephrine cartridges, but not with collagen/ADP cartridges. The average duration from drug cessation until return of closure times (collagen/epinephrine cartridges) to baseline values was 11.6, 10.6, 11 and 10.6 days for carprofen (2.2 mg kg^?1 every 12 hours), carprofen (4.4 mg kg^?1 every 24 hours), meloxicam and deracoxib, respectively.Conclusions and clinical relevanceOral administration of some COX-2 selective NSAIDs causes detectable alterations in platelet function in dogs. As in humans, PFA-100 collagen/ADP cartridges do not reliably detect COX-mediated platelet dysfunction in dogs. Individual assessment of platelet function is advised when administering these drugs prior to surgery, particularly in the presence of other risk factors for bleeding.     

Postoperative bleeding in retired racing greyhounds

BACKGROUND: Some retired racing Greyhounds (RRG) that undergo surgery bleed excessively. Hypothesis: Greyhounds that bleed excessively will have one or more preoperative hemostatic abnormalities that can be used to predict the risk and severity of postoperative bleeding. ANIMALS: Eighty-eight RRG undergoing ovariohysterectomy or castration. METHODS: All dogs were evaluated preoperatively with a physical exam, CBC, platelet count, OSPT, APTT, platelet function with PFA-100(a); fibrinogen, d-dimer, plasminogen (Plmg), antiplasmin (AP), antithrombin (AT), and vWF concentration (vWF:Ag); vWF collagen binding assay (vWF:CBA), and Factor XIII assay. Assays were repeated in the dogs that bled, and in an age- and sex-matched control group of RRG. RESULTS: Twenty-six percent of the dogs had bleeding 36-48 hours after surgery. AP (P <.0001) and AT concentration (P= .007) were significantly lower, and vWF:CBA (P= .0284) was higher preoperatively in the dogs with excessive hemorrhage. A lower platelet count (P= .001) and hematocrit (P= .002), shorter OSPT (P= .0002) and higher plasma fibrinogen (P <.0001), and AP (P= .001) concentration were detected at the time of bleeding compared with preoperative values in the dogs that bleed excessively. The same findings were observed postoperatively for the control group, except for the decrease in hematocrit. CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that this excessive postoperative bleeding is not attributable to a primary or secondary hemostatic defect, but could result from altered fibrinolysis.     

Buccal mucosa bleeding times of healthy dogs and of dogs in various pathologic states, including thrombocytopenia, uremia, and von Willebrand's disease

The buccal mucosa bleeding time (BMBT; duration of hemorrhage from standardized cuts made with a spring-loaded disposable device in the mucosal surface of the upper lip) was used to evaluate the hemostatic competence of dogs. The mean (+/- SD) BMBT for 34 healthy dogs was 2.62 +/- 0.49 minutes. The BMBT of healthy dogs anesthetized with halothane or tranquilized with xylazine were not significantly different from the BMBT of healthy dogs evaluated without chemical restraint. The BMBT was significantly (P less than 0.01) prolonged 21 hours after aspirin (10 mg/kg of body weight) was administered orally to 10 healthy dogs; however, the mean aspirin-induced increase in BMBT was only 0.40 minutes. The BMBT of 28 of 30 dogs with various diseases not traditionally associated with hemostatic deficiencies were near or within the range of BMBT for healthy dogs; however, 2 dogs had BMBT of greater than 8 minutes. In contrast, BMBT were prolonged in most dogs with diseases known to induce deficient primary hemostasis; the 3 dogs with thrombocytopenia (less than or equal to 20,000 platelets/microliter), the 7 Doberman Pinschers with von Willebrand's disease (von Willebrand factor antigen; less than or equal to 18 U/dl), and 5 of the 6 dogs with severe azotemia (serum urea nitrogen; greater than or equal to 124 mg/dl) had prolonged BMBT. The BMBT of 16 dogs were determined immediately before they were subjected to various surgical procedures, and the severity of the hemorrhage encountered during these procedures was subjectively evaluated; the amount of hemorrhage from 12 of the 16 dogs was considered to be appropriate for the corresponding surgical procedures, but the remaining 4 dogs bled excessively during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of desmopressin on immune-mediated haemorrhagic disorders due to canine monocytic ehrlichiosis: a preliminary study

To evaluate the possible use of desmopressin acetate (DDAVP) in haemorrhagic disorders consequent to canine monocytic ehrlichiosis (CME), three dogs infected by Ehrlichia canis, with a history of thrombocytopenia and recent bleeding, were studied. The dogs were administered desmopressin (1 μg/kg b.w. s.c.) every 24 h on three occasions. Blood samples were collected immediately before, and after 2 and 48 h the first DDAVP administration, to assess haematological, clinical chemistry and clotting time parameters. Spontaneous bleeding stopped within 1 h after the first DDAVP injection. Buccal mucosa bleeding time (BMBT) was shortened from 9.6 to 2.3 min within 2 h after the treatment. A statistically significant increase in platelet PLT count and fibrinogen, and a statistically significant decrease of PT and aPTT were observed after DDAVP administration. The haemorrhagic disorders caused by CME appear to be quickly corrected by DDAVP administration, giving the clinician the time necessary to administer appropriate chemotherapy.     

Effects of lactated Ringer solution and prednisolone sodium succinate on dogs with induced hemorrhagic shock.

Hemorrhagic shock was induced in nonsplenectomized dogs by removing 41% of their blood volume over a 15-minute period. Hemodynamic and metabolic variables were determined prior to and for 3 hours after completion of hemorrhage. One group of 5 dogs was not treated. After the 30-minute sample was collected, a second group of 5 dogs was given lactated Ringer solution (LRS) at 88 ml/kg of body weight, IV. A third group of 5 dogs was given LRS (88 ml/kg, IV) and prednisolone sodium succinate (11 mg/kg, IV) 30 minutes after hemorrhage. The IV administration of LRS was completed within 15 minutes. The glucocorticoid was administered as an IV bolus after 500 ml of LRS had been given. The large volume and administration of LRS significantly (P = 0.05) improved many of the hemodynamic and metabolic effects of acute hemorrhage and hemorrhagic shock. At one time or another during the 2.5-hour observation period after the initiation of treatment, mean arterial pressure, cardiac index, systemic vascular resistance, heart rate, respiratory rate, lactate, glucose, and arterial and venous blood gas values were significantly (P = 0.05) improved, compared with baseline values. The addition of prednisolone sodium succinate to the treatment regimen improved the effectiveness of LRS alone only in some dogs at random sampling times. Significant trends were not observed except, possibly, the improvement of venous pH and A-V pH and PCO2 differences.     

Analgesic effect of pre-operative etodolac and butorphanol administration in dogs undergoing ovariohysterectomy

The analgesic, bleeding, and renal effects of dogs pre‐medicated with etodolac with and without butorphanol were evaluated. Twenty‐four 1‐year‐old healthy dogs, weighing 19 ± 3 kg (mean ± SD) were randomly assigned to four treatment groups (n = 6): control (C), etodolac (E), butorphanol (B), and etodolac with butorphanol (EB). Etodolac (12–14 mg kg^?1 PO) was given 1 hour before propofol induction and isoflurane maintenance anesthesia. Butorphanol (0.4 mg kg^?1 IV) was given immediately following endotracheal intubation. Control dogs received only propofol (8 mg kg^?1 to effect) and isoflurane anesthesia. All dogs were mechanically ventilated to maintain Pe ′CO₂ between 35 and 45 mm Hg (4.7–6.0 kPa). Lactated Ringer's solution was given at 10 mL kg^?1 hour^?1 during anesthesia. Plasma cortisol concentrations were assessed 1 day prior to surgery (baseline), immediately prior to anesthesia induction, and every 30 minutes until 5 hours following extubation, and 1 day after surgery. Total duration of anesthesia was 50 minutes and total surgery duration was 30 minutes. Isoflurane concentration area under the curve (AUC) over time during the anesthesia was compared among treatment groups. Buccal mucosal bleeding time (BMBT) was assessed 1 day before E administration and during surgery. Urine GGT to urine creatinine ratio, BUN, and plasma creatinine were taken daily from 1 day before to 3 days after surgery. Behavioral pain scores (numerical rating scale) were assessed by two observers blinded to the treatment during the 5‐hour recovery period at 30 minute intervals until 3 hours, and again at 5 hours after extubation. All data were analyzed using anova . Multiple comparisons were performed if the anova was significant. Alpha value was set at 0.05. Plasma cortisol concentrations significantly increased from time of extubation in all the treatment groups. They did not return to the baseline until 5, 2.5, 1.5, and 1.5 hours after extubation in the C, B, E, and EB groups, respectively. Isoflurane AUC was not significantly different among treatment groups. Dogs treated with EB had significantly less behavioral pain than all other groups throughout the 5‐hour recovery period. No significant difference was found between treatment groups or within treatment groups over time in BMBT, or any renal variables. This study demonstrated that (i) pre‐operative administration of E provides profound analgesia during the post‐operative period without renal or bleeding side‐effects in dogs undergoing OHE; and (ii) a combination of butorphanol–etodolac provides the best analgesic effect during the post‐operative period based on the behavioral pain score.     

The Effect of Hetastarch on Serum Colloid Oncotic Pressure in Hypoalbuminemic Dogs

The purpose of this study was to determine the duration of action of a single dose of hetastarch, a synthetic colloid, in hypoalbuminemic dogs. Thirty hypoalbuminemic dogs (albumin concentration, 2,0 g/dL) received 1 dose of hetastarch each, with an average dose of 18.1 mL/kg. Doses ranged from 7.7 to 43.9 mL/kg, with the majority of doses (n = 26) in the range of 10 to 25 mL/kg. Dogs were allotted to one of several groups: all dogs, dogs with acute gastrointestinal protein loss, dogs with chronic gastrointestinal protein loss, all dogs with gastrointestinal protein loss, and dogs with nongastrointestinal protein loss. Colloid oncotic pressure was measured immediately before and immediately after hetastarch administration, and 12 hours after hetastarch administration. There was a significant ( P < .001) increase in the mean colloid oncotic pressure after hetastarch treatment in all groups, except in the group with acute gastrointestinal protein loss. Twelve hours after hetastarch treatment, the mean colloid oncotic pressure had decreased significantly ( P < .001) from the immediate post-treatment value in all groups, except in dogs in the groups with acute and chronic gastrointestinal protein loss. Twelve hours after hetastarch treatment the mean colloid oncotic pressure was not significantly ( P < .001) different from the baseline mean colloid oncotic pressure in any of the groups. Twenty-three dogs (77%) survived their illness and were sent home, whereas, 7 (23%) died or were euthanized. The effect of a single dose of hetastarch on raising colloid oncotic pressure in dogs with hypoalbuminemia decreases significantly within 12 hours of administration, and is no longer significantly above baseline values. We conclude that multiple dosing is necessary to prolong the beneficial effects of hetastarch.     

Prophylactic use of a lidocaine constant rate infusion versus saline in dogs undergoing balloon valvuloplasty for management of pulmonic stenosis: A randomized control trial

ObjectiveTo evaluate the effect of a prophylactic lidocaine constant rate infusion (CRI) on the incidence and malignancy of catheter-induced ventricular ectopic complexes (VECs) during balloon valvuloplasty for management of pulmonic stenosis in dogs.Study designSingle-centre, prospective, randomized study.AnimalsClient-owned dogs (n = 70) with pulmonic stenosis.MethodsDogs were randomly assigned to one of two anaesthetic protocols: administration of lidocaine 2 mg kg^–1 bolus followed by a CRI (50 μg kg^–1 minute^–1; group LD) or a saline placebo (group SL) during balloon valvuloplasty. All dogs were premedicated with methadone (0.3 mg kg^–1) intramuscularly and a digital three-lead Holter monitor was applied. Anaesthetic co-induction was performed with administration of alfaxalone (2 mg kg^–1) and diazepam (0.4 mg kg^–1), and anaesthesia was maintained with isoflurane vaporised in 100% oxygen. CRIs were started on positioning of the dog in theatre and discontinued as the last vascular catheter was removed from the heart. All dogs recovered well and were discharged 24 hours postoperatively. Blinded Holter analysis was performed by an external veterinary cardiologist using commercially available dedicated analysis software; p < 0.05.ResultsOf the 70 dogs enrolled in the study, 61 were included in the final analysis: 31 in group LD and 30 in group SL.There was no significant difference between sinus beats (p = 0.227) or VECs (p = 0.519) between groups. In group LD, 19/31 (61.3%) dogs had a maximum ventricular rate ≥250 units and 20/30 (66.7%) dogs in group SL (p = 0.791).Conclusion and clinical relevanceIn this study, the use of a prophylactic lidocaine bolus followed by CRI in dogs undergoing balloon valvuloplasty for management of pulmonic stenosis did not significantly decrease the incidence nor the malignancy of VECs during right heart catheterization compared with a saline CRI.     

Use of intravenous lidocaine to treat dexmedetomidine-induced bradycardia in sedated and anesthetized dogs

ObjectiveTo assess cardiopulmonary function in sedated and anesthetized dogs administered intravenous (IV) dexmedetomidine and subsequently administered IV lidocaine to treat dexmedetomidine-induced bradycardia.Study designProspective, randomized, crossover experimental trial.AnimalsA total of six purpose-bred female Beagle dogs, weighing 9.1 ± 0.6 kg (mean ± standard deviation).MethodsDogs were randomly assigned to one of three treatments: dexmedetomidine (10 μg kg^–1 IV) administered to conscious (treatments SED1 and SED2) or isoflurane-anesthetized dogs (end-tidal isoflurane concentration 1.19 ± 0.04%; treatment ISO). After 30 minutes, a lidocaine bolus (2 mg kg^–1) IV was administered in treatments SED1 and ISO, followed 20 minutes later by a second bolus (2 mg kg^–1) and a 30 minute lidocaine constant rate infusion (L-CRI) at 50 (SED1) or 100 μg kg^–1 minute^–1 (ISO). In SED2, lidocaine bolus and L-CRI (50 μg kg^–1 minute^–1) were administered 5 minutes after dexmedetomidine. Cardiopulmonary measurements were obtained after dexmedetomidine, after lidocaine bolus, during L-CRI and 30 minutes after discontinuing L-CRI. A mixed linear model was used for comparisons within treatments (p < 0.05).ResultsWhen administered after a bolus of dexmedetomidine, lidocaine bolus and L-CRI significantly increased heart rate and cardiac index, decreased mean blood pressure, systemic vascular resistance index and oxygen extraction ratio, and did not affect stroke volume index in all treatments.Conclusion and clinical relevanceLidocaine was an effective treatment for dexmedetomidine-induced bradycardia in healthy research dogs.     

Cardiovascular effects of dobutamine,norepinephrine and phenylephrine in isoflurane-anaesthetized dogs administered dexmedetomidine–vatinoxan

ObjectiveTo determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan.Study designBalanced, randomized crossover trial.AnimalsA total of eight healthy Beagle dogs.MethodsEach dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 μg kg^–1) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 μg kg^–1) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used.ResultsMost dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 μg kg^–1 minute^–1 for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute^–1 m^–2, respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute^–1 m^–2).Conclusions and clinical relevanceHypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.     

Type III von Willebrand's disease in Dutch kooiker dogs

Summary

Type III von Willebrand's disease (vWD) was diagnosed in 38 Dutch kooiker dogs. Ten male and 9 female probands had been referred independently of each other to the Utrecht University Clinic for Companion Animals because of a moderate to severe bleeding tendency. Screening of 717 Dutch kooiker dogs, including 356 puppies, detected vWD in another 19 dogs. Diagnosis was based on non‐detectable amounts (< 1.6%) of von Willebrand factor antigen (vWF:Ag) in plasma by ELISA. Capillary bleeding time (CBT) was prolonged (> 10 min) and polybrene cofactor activity (vWF:PbCo) was not detectable in 11 dogs tested. No distinguishable protein bands were detected by multimer analysis. As in Scottish terriers with type III vWD, factor VIII clotting activity (F_VIII:C) in affected Dutch kooiker dogs was decreased but considerably less than in humans with type III vWD. A recessive mode of inheritance was indicated by the normal or subnormal but measurable amounts of vWF:Ag in the plasma of eight pairs of parents of affected dogs. The F₁ offspring resulting from the experimental mating of two affected dogs consisted of three affected males and four affected females. In 39 obligatory carriers vWF:Ag ranged from 30% to 114% with median and mean vWF values of 64% and 64.2%, respectively, and was subnormal (< 50%) in only 9 animals.     

Pharmacokinetics of single-dose oral pregabalin administration in normal dogs

ObjectiveTo describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.Study designProspective experiment.AnimalsSix adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6–5.6) years old (median and range) weighing 33.4 (26.8–42.1) kg.MethodsAfter jugular vein catheterization, the dogs received a single oral dose of pregabalin (～4 mg kg^?1). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.ResultsNo adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5–92.1) μg hour mL^?1; absorption half-life = 0.38 (0.25–1.11) hours; elimination half-life = 6.90 (6.21–7.40) hours; time over 2.8 μg mL^?1 (the presumed minimal effective concentration) = 11.11 (6.97–14.47) hours; maximal plasma concentration (C_max) = 7.15 (4.6–7.9) μg mL^?1; time for C_max to occur = 1.5 (1.0–4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8–8.1), 8.8 (7.3–10.9), and 13.0 (8.8–15.2) μg mL^?1. The corresponding values assuming a 12-hour interval were 3.8 (2.4–4.8), 6.8 (4.9–7.9), and 10.1 (6.6–11.6) μg mL^?1.Conclusions and clinical relevancePregabalin 4 mg kg^?1 PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.     

Postoperative analgesic effects of either a constant rate infusion of fentanyl,lidocaine, ketamine,dexmedetomidine, or the combination lidocaine‐ketamine‐dexmedetomidine after ovariohysterectomy in dogs

ObjectiveTo evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs.Study designRandomized, prospective, blinded, clinical study.AnimalsFifty-four dogs.MethodsAnesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg⁻¹, infusion rate of saline 0.9% 2 mLkg⁻¹ hour⁻¹); FENT (5 μg kg⁻¹, 10 μg kg⁻¹hour⁻¹, then 2.5 μg kg⁻¹ hour⁻¹); KET (1 mgkg⁻¹, 40 μg kg⁻¹ minute⁻¹, then 10 μg kg⁻¹minute⁻¹); LIDO (2 mg kg⁻¹, 100 μg kg⁻¹ minute⁻¹, then 25 μg kg⁻¹ minute⁻¹); DEX (1 μgkg⁻¹, 3 μg kg⁻¹ hour⁻¹, then 1 μg kg⁻¹ hour⁻¹); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal–Wallis test with appropriate post-hoc testing (p < 0.05).ResultsAnimals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour.Conclusions and clinical relevanceLKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.     

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs

ObjectiveTo compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated.Study designProspective, randomised, blinded, positive-controlled parallel-group clinical study.AnimalsForty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery.MethodsAfter surgery, a loading dose of either DMED (25 μg m^?2) or MOR (2500 μg m^?2) followed by a 24-hour CRI of DMED (25 μg m^?2 hour^?1) or MOR (2500 μg m^?2 hour^?1) was administered. Pain was measured using the Short Form of the Glasgow Composite Measure Pain Scale, sedation and physiological variables were scored at regular intervals. Animals considered to be painful received rescue analgesia and were allocated to a post-rescue protocol; animals which were unresponsive to rescue analgesia were removed from the study. Data were analysed with anova, two-sample t-tests or Chi-square tests. Time to intervention was analysed with Kaplan–Meier methodology.ResultsForty dogs were enrolled. Twenty dogs (9 DMED and 11 MOR) did not require rescue analgesia. Eleven DMED and eight MOR dogs were allocated to the post-rescue protocol and seven of these removed from the study. Significant differences in pain scores between groups were not observed during the first 12 hours, however, DMED dogs were less (p = 0.009) painful during the last 12 hours. Sedation score over the entire 24-hour study was not significantly different between groups.Conclusion / Clinical RelevanceDexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted. This study shows the potential of DMED to contribute to a balanced postoperative analgesia regimen in dogs.     

Effect of levothyroxine administration on hemostatic analytes in Doberman Pinschers with von Willebrand disease

Levothyroxine administration has been suggested to be an effective treatment for canine von Willebrand disease (vWd), but evidence supporting this treatment is lacking. Effects of levothyroxine administration were evaluated in 8 euthyroid Doberman Pinschers with plasma von Willebrand factor (vWf) concentrations < 15%, characteristic of type 1 vWd. Levothyroxine (0.04 mg/kg PO q12h) and placebo were administered for 30 days in a 2-period, 2-treatment, double-blinded, crossover design with a 30-day washout period between treatments. Buccal mucosal bleeding time (BMBT), plasma vWf concentration (vWf: Ag), vWf collagen binding activity (vWf:CBA), factor VIII coagulant activity (FVIII:C), and serum concentrations of total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured on days 0, 2, and 30 of each treatment period. The 8 dogs (1 male, 7 females) had markedly low plasma vWf:Ag (mean, 8.9%; reference range, 70-180%) and vWf:CBA (mean, 11.1%; reference range, >70%). Response to placebo versus levothyroxine treatment was not significantly different between groups at day 0, 2, or 30 for BMBT, vWf:Ag, vWf:CBA, and FVIII:C. Serum T4, fT4, and T3 concentrations were significantly higher and serum TSH significantly lower in the levothyroxine-treated group than in the placebo group at days 2 and 30. Administration of levothyroxine at 0.04 mg/kg caused laboratory evidence of hyperthyroidism but did not affect plasma FVIII:C and vWf:Ag concentrations or vWf-dependent collagen binding and BMBT. The results of this study failed to identify a direct action of levothyroxine supplementation on plasma vWf concentration or activity in euthyroid Doberman Pinschers with vWd.