Marie K. Holowaychuk

Systematic evaluation of evidence on veterinary viscoelastic testing part 4: Definitions and data reporting.

Objective To systematically examine evidence surrounding definitions and reporting of data for viscoelastic testing in veterinary medicine. Design Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Setting Academic and referral veterinary medical centers. Results Databases searched included Medline, CAB abstracts, and Google Scholar. Conclusions All 4 standard thromboelastography (TEG) and rotational thromboelastometry (ROTEM) variables should be universally reported, and the reporting of shear elastic modulus in addition to maximum amplitude (MA) is encouraged. There is insufficient evidence to support universal usage of the coagulation index at this time. The K value and clot formation time are the most variable of the 4 parameters, with alpha angle, MA, and maximum clot firmness generally the least variable. Individual studies should report sufficient data on patients and institutional controls to enable definitions of hypo- and hypercoagulability to be evaluated post-hoc, and it is recommended that all studies specifically report how these conditions were defined. In reporting data relating to fibrinolysis, the TEG variables LY30, LY60, CL30, CL60, and the ROTEM variables LI30, LI60, ML, LOT, and LT should be documented. Studies should report sufficient data on patients and controls to enable definitions of hyper- and hypofibrinolysis to be evaluated post-hoc, and we suggest that standard TEG/ROTEM assays may be unable to detect hypofibrinolysis in companion animals. We recommend that every center establish reference intervals, which are specific to either TEG or ROTEM. These reference intervals should be established using veterinary clinical pathology guidelines, standardized protocols, and a minimum of 40 healthy animals. There are currently insufficient data in companion animals to suggest a utility for Vcurve variables beyond that of standard TEG variables.OBJECTIVE To systematically examine evidence surrounding definitions and reporting of data for viscoelastic testing in veterinary medicine. DESIGN Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. SETTING Academic and referral veterinary medical centers. RESULTS Databases searched included Medline, CAB abstracts, and Google Scholar. CONCLUSIONS All 4 standard thromboelastography (TEG) and rotational thromboelastometry (ROTEM) variables should be universally reported, and the reporting of shear elastic modulus in addition to maximum amplitude (MA) is encouraged. There is insufficient evidence to support universal usage of the coagulation index at this time. The K value and clot formation time are the most variable of the 4 parameters, with alpha angle, MA, and maximum clot firmness generally the least variable. Individual studies should report sufficient data on patients and institutional controls to enable definitions of hypo- and hypercoagulability to be evaluated post-hoc, and it is recommended that all studies specifically report how these conditions were defined. In reporting data relating to fibrinolysis, the TEG variables LY30, LY60, CL30, CL60, and the ROTEM variables LI30, LI60, ML, LOT, and LT should be documented. Studies should report sufficient data on patients and controls to enable definitions of hyper- and hypofibrinolysis to be evaluated post-hoc, and we suggest that standard TEG/ROTEM assays may be unable to detect hypofibrinolysis in companion animals. We recommend that every center establish reference intervals, which are specific to either TEG or ROTEM. These reference intervals should be established using veterinary clinical pathology guidelines, standardized protocols, and a minimum of 40 healthy animals. There are currently insufficient data in companion animals to suggest a utility for Vcurve variables beyond that of standard TEG variables.

Prospective multicenter evaluation of coagulation abnormalities in dogs following severe acute trauma

OBJECTIVES To describe coagulation abnormalities in dogs following severe acute trauma and to evaluate the relationship between coagulation, clinical, and laboratory variables, and disease and injury severity, as well as the ability of coagulation variables to predict the presence of body cavity hemorrhage (BCH), necessity of blood product administration, and outcome. DESIGN Prospective, multicenter, observational study. SETTING Two university teaching hospitals. ANIMALS Forty client-owned dogs sustaining severe blunt or penetrating trauma. INTERVENTIONS Blood samples were collected within 12 hours of the traumatic incident for measurement of blood gases, lactate concentration, platelet count, activated clotting time, prothrombin time, activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin activity, D-dimer concentration, protein C activity, plasmin inhibition, plasminogen activity, and kaolin-activated thomboelastography. RESULTS Decreased platelet count was a risk factor for the presence of BCH (P = 0.006) and decreased platelet count (P < 0.001), protein C activity (P = 0.001), angle (α) (P = 0.001), maximum amplitude (MA) (P < 0.001), and clot strength (G) (P = 0.002) were risk factors for blood product administration. Nonsurviving dogs were hypocoagulable with prolonged aPTT (P = 0.008), decreased plasmin inhibition (P = 0.033), decreased α (P = 0.021), and decreased MA (P = 0.038) compared to surviving dogs. Multivariate analysis accounting for disease severity showed that prolonged aPTT (P = 0.004, OR = 1.74) was the strongest predictor of nonsurvival. Prolonged aPTT was positively correlated with APPLE-fast score (P < 0.001, r(2) = 0.35), lactate concentration (P < 0.001, r(2) = 0.35), and negative base excess (P = 0.001, r(2) = 0.27). Acute traumatic coagulopathy, as defined by 2 or more abnormal coagulation tests, was diagnosed in 15% of dogs at hospital admission and was more common in dogs with increased disease severity (P = 0.002), decreased systolic blood pressure (P = 0.002), and increased lactate concentration (P = 0.011). CONCLUSIONS In dogs with severe traumatic injuries and hypoperfusion, measurement of thromboelastography and aPTT should be considered to support clinical assessments in predicting the need for blood product administration and nonsurvival.

Effect of synthetic colloid administration on hemodynamic and laboratory variables in healthy dogs and dogs with systemic inflammation.

Objective To compare the effects of administering equal volumes of isotonic crystalloids and synthetic colloids on hemodynamic and laboratory variables in healthy dogs and dogs with systemic inflammation. Design Randomized, placebo-controlled, blinded study. Setting Comparative clinical research facility. Animals Sixteen adult purpose-bred Beagles. Interventions Dogs were first randomized to receive either lipopolysaccharide (LPS; 5 μg/kg, IV) or an equal volume of placebo (0.9% NaCl, IV). Dogs were then randomized into 1 of 2 groups receiving fluid resuscitation with either 40 mL/kg IV isotonic crystalloid (0.9% NaCl) or synthetic colloid (tetrastarch). After a 14-day washout, the study was repeated such that dogs received the opposite treatment (LPS or placebo) and the same resuscitation fluid regimen. Vital signs (heart rate (HR), oscillometric blood pressure) were measured and blood samples were collected for PCV, total plasma protein (TPP), serum lactate concentration, and colloid osmotic pressure (COP) measurements. Measurements and Main Results Healthy (placebo) dogs had similar decreases in PCV and TPP after administration of either fluid. Tetrastarch administration was associated with a larger increase in HR, systolic blood pressure, and mean blood pressure. Dogs with systemic inflammation had similar increases in systolic blood pressure and decreases in PCV, TPP, and lactate after administration of either fluid. Tetrastarch administration caused greater immediate increase in HR and mean blood pressure compared to 0.9% NaCl. In all dogs, 0.9% NaCl administration decreased COP and tetrastarch administration increased COP. Conclusions Resuscitation with equal volumes of 0.9% NaCl and tetrastarch caused similar changes in hemodynamic and laboratory variables in dogs with LPS-induced systemic inflammation; however, larger increases in HR and blood pressure were seen within the first 2 hours following tetrastarch administration compared to 0.9% NaCl. Tetrastarch administration increased COP in all dogs, despite a decrease in TPP.OBJECTIVE To compare the effects of administering equal volumes of isotonic crystalloids and synthetic colloids on hemodynamic and laboratory variables in healthy dogs and dogs with systemic inflammation. DESIGN Randomized, placebo-controlled, blinded study. SETTING Comparative clinical research facility. ANIMALS Sixteen adult purpose-bred Beagles. INTERVENTIONS Dogs were first randomized to receive either lipopolysaccharide (LPS; 5 μg/kg, IV) or an equal volume of placebo (0.9% NaCl, IV). Dogs were then randomized into 1 of 2 groups receiving fluid resuscitation with either 40 mL/kg IV isotonic crystalloid (0.9% NaCl) or synthetic colloid (tetrastarch). After a 14-day washout, the study was repeated such that dogs received the opposite treatment (LPS or placebo) and the same resuscitation fluid regimen. Vital signs (heart rate (HR), oscillometric blood pressure) were measured and blood samples were collected for PCV, total plasma protein (TPP), serum lactate concentration, and colloid osmotic pressure (COP) measurements. MEASUREMENTS AND MAIN RESULTS Healthy (placebo) dogs had similar decreases in PCV and TPP after administration of either fluid. Tetrastarch administration was associated with a larger increase in HR, systolic blood pressure, and mean blood pressure. Dogs with systemic inflammation had similar increases in systolic blood pressure and decreases in PCV, TPP, and lactate after administration of either fluid. Tetrastarch administration caused greater immediate increase in HR and mean blood pressure compared to 0.9% NaCl. In all dogs, 0.9% NaCl administration decreased COP and tetrastarch administration increased COP. CONCLUSIONS Resuscitation with equal volumes of 0.9% NaCl and tetrastarch caused similar changes in hemodynamic and laboratory variables in dogs with LPS-induced systemic inflammation; however, larger increases in HR and blood pressure were seen within the first 2 hours following tetrastarch administration compared to 0.9% NaCl. Tetrastarch administration increased COP in all dogs, despite a decrease in TPP.

Risk factors for transfusion-associated complications and nonsurvival in dogs receiving packed red blood cell transfusions: 211 cases (2008-2011)

OBJECTIVE To determine whether the number, volume, or age of transfused packed RBC units; volume of other blood products; or pretransfusion PCV was a risk factor for transfusion-associated complications or nonsurvival in dogs. DESIGN Retrospective case series. ANIMALS 211 client-owned dogs receiving stored packed RBC transfusions. PROCEDURES Information collected or calculated from the medical record of each dog included the total number, volume, and dose of packed RBC units; mean age of packed RBC units; number of packed RBC units > 14 days old; age of oldest packed RBC unit; volume and dose of other blood products used; pretransfusion PCV; acute patient physiologic and laboratory evaluation score; transfusion-associated complications; and outcome. RESULTS The dose (mL/kg) of other blood products transfused was a risk factor for transfusion-associated complications (OR, 1.03; 95% confidence interval [CI], 1.01 to 1.05). The pretransfusion PCV (OR, 1.13; 95% CI, 1.06 to 1.21) and dose of packed RBCs administered (OR, 1.04; 95% CI, 1.02 to 1.07) were risk factors for nonsurvival. Age of transfused packed RBC units was not identified as a risk factor for transfusion-associated complications or nonsurvival, but the study was statistically underpowered to detect this finding. CONCLUSIONS AND CLINICAL RELEVANCE Administration of larger doses of other non-packed RBC blood products was a risk factor for transfusion-associated complications, and a higher pretransfusion PCV and larger dose of packed RBCs administered were risk factors for nonsurvival. Prospective randomized studies are needed to determine whether conservative transfusion strategies will reduce transfusion-associated complications and improve outcome in dogs.

Transfusion practice in dogs and cats: an Internet-based survey.

OBJECTIVE To characterize and compare current canine and feline transfusion practices at private referral hospitals (PRH) and veterinary teaching hospitals (VTH), including information regarding blood donor screening; blood product collection, storage, and administration; recipient screening; and monitoring during transfusions. DESIGN Internet-based survey. SUBJECTS Sixty-five board-certified specialist veterinarians, 3 veterinarians, and 5 veterinary technicians from 53 PRH and 20 VTH. METHODS A survey was disseminated via email LIST-SERVs; 1 survey response per hospital was included. MAIN RESULTS Survey results revealed that PRH more commonly obtained canine and feline blood products solely from blood banks (P < 0.05) and VTH more commonly used hospital-run donor programs (P < 0.05). Canine cryo-poor plasma was more likely to be stored by VTH compared to PRH (P = 0.018) and VTH were more likely to store canine fresh platelet products for >72 hours (P = 0.046). The use of client-owned canine donors (P = 0.043), administration of precollection 1-deamino-8-d-arginine vasopressin to canine donors (P = 0.041), and storage of blood products in a dedicated refrigerator (P = 0.003) and -20°C or -80°C freezer (P = 0.044) were more common in VTH than PRH. However, the use of a refrigerator freezer (P = 0.001), single bag canine collection systems (P = 0.021), and agglutination cards for feline blood typing (P = 0.032), as well as warming of blood products prior to administration (P = 0.021) were more commonly reported by PRH compared to VTH. CONCLUSIONS Although some transfusion practices including the method and length of storage of blood products, use and screening of blood donors, and administration methods varied between VTH and PRH, most transfusion practices were similar. The information reported from this survey could aid the development of future veterinary transfusion consensus statements.Objective To characterize and compare current canine and feline transfusion practices at private referral hospitals (PRH) and veterinary teaching hospitals (VTH), including information regarding blood donor screening; blood product collection, storage, and administration; recipient screening; and monitoring during transfusions. Design Internet-based survey. Subjects Sixty-five board-certified specialist veterinarians, 3 veterinarians, and 5 veterinary technicians from 53 PRH and 20 VTH. Methods A survey was disseminated via email LIST-SERVs; 1 survey response per hospital was included. Main Results Survey results revealed that PRH more commonly obtained canine and feline blood products solely from blood banks (P 72 hours (P = 0.046). The use of client-owned canine donors (P = 0.043), administration of precollection 1-deamino-8-d-arginine vasopressin to canine donors (P = 0.041), and storage of blood products in a dedicated refrigerator (P = 0.003) and −20°C or −80°C freezer (P = 0.044) were more common in VTH than PRH. However, the use of a refrigerator freezer (P = 0.001), single bag canine collection systems (P = 0.021), and agglutination cards for feline blood typing (P = 0.032), as well as warming of blood products prior to administration (P = 0.021) were more commonly reported by PRH compared to VTH. Conclusions Although some transfusion practices including the method and length of storage of blood products, use and screening of blood donors, and administration methods varied between VTH and PRH, most transfusion practices were similar. The information reported from this survey could aid the development of future veterinary transfusion consensus statements.

Intravenous administration of desmopressin acetate to reverse acetylsalicylic acid-induced coagulopathy in three dogs

BACKGROUND Acetylsalicylic acid (ie, aspirin) administration inhibits platelet aggregation in dogs and is associated with increased perioperative blood loss and transfusion requirements in people. Desmopressin acetate (DDAVP) is used to control or prevent bleeding in dogs with type 1 von Willebrand disease and is also widely reported in the human literature as an emergency antithrombotic reversal agent. KEY FINDINGS Three dogs undergoing surgery for intervertebral disc disease had marked prolongations in buccal mucosal bleeding time (BMBT) after aspirin administration. DDAVP was given intravenously preoperatively and achieved prompt reversal of the prolongation in BMBT. None of the dogs experienced intraoperative bleeding complications. SIGNIFICANCE IV DDAVP corrected prolongations in BMBT in dogs given aspirin and should be considered in dogs requiring prompt reversal of aspirin-induced coagulopathies to reduce the risk of bleeding complications.

A comparison of 3 anesthetic protocols for 24 hours of mechanical ventilation in cats

Objective To compare the recovery times, recovery quality, and cardiovascular (CV) effects of 3 anesthetic protocols during 24 hours of mechanical ventilation (MV) in healthy cats. Design Prospective, randomized, crossover study. Setting Research laboratory at a veterinary teaching hospital. Animals Six healthy intact male purpose-bred cats. Interventions Each cat was randomly assigned to receive 3 anesthetic protocols for 24 hours of MV; Protocol K consisted of ketamine, Protocol P, propofol; and Protocol PK, propofol plus fixed-rate low-dose ketamine. Each infusion drug dose was adjusted using a sedation scoring system. All protocols included fixed doses of fentanyl (10 μg/kg/h) and midazolam (0.5 mg/kg/h). Measurements and Main Results Drug doses and recovery times were recorded. Recovery quality was scored. Blood gas results, CV parameters, and frequency of bradycardia or hypotension requiring interventions were recorded. The mean d dose ± standard error of K was 81.3 ± 3.3 μg/kg/m. The median dose (95% cardiac index) of propofol (μg/kg/m) in PK was 16.0 (13.1, 19.6) and in P was 48.1 (39.3, 58.9). P necessitated significantly more propofol than PK (P < 0.05). Protocol K (35.6 ± 3.2 hours) had significantly longer times to full recovery compared to P (18.2 ± 3.2 hours). Protocol K had significantly longer times to head up, crawling, and standing compared to P and PK. Cats sedated with PK (2.33 ± 0.47) required significantly more interventions for hypotension than K (0.50 ± 0.47). Protocol P (3.2 ± 0.4) and PK (1.4 ± 0.3) required significantly more interventions for bradycardia compared to K (0.8 ± 0.3). When comparing protocol K to P and PK, significant differences in blood pressure, lactate, oxygen delivery, and oxygen consumption were noted. Conclusions Cats anesthetized with P had shorter times to full recovery compared to K. Cats anesthetized with K required fewer interventions for bradycardia or hypotension but had longer recovery times compared to P or PK. Protocol PK reduced the propofol dose required to maintain optimal anesthesia.OBJECTIVE To compare the recovery times, recovery quality, and cardiovascular (CV) effects of 3 anesthetic protocols during 24 hours of mechanical ventilation (MV) in healthy cats. DESIGN Prospective, randomized, crossover study. SETTING Research laboratory at a veterinary teaching hospital. ANIMALS Six healthy intact male purpose-bred cats. INTERVENTIONS Each cat was randomly assigned to receive 3 anesthetic protocols for 24 hours of MV; Protocol K consisted of ketamine, Protocol P, propofol; and Protocol PK, propofol plus fixed-rate low-dose ketamine. Each infusion drug dose was adjusted using a sedation scoring system. All protocols included fixed doses of fentanyl (10 μg/kg/h) and midazolam (0.5 mg/kg/h). MEASUREMENTS AND MAIN RESULTS Drug doses and recovery times were recorded. Recovery quality was scored. Blood gas results, CV parameters, and frequency of bradycardia or hypotension requiring interventions were recorded. The mean d dose ± standard error of K was 81.3 ± 3.3 μg/kg/m. The median dose (95% cardiac index) of propofol (μg/kg/m) in PK was 16.0 (13.1, 19.6) and in P was 48.1 (39.3, 58.9). P necessitated significantly more propofol than PK (P < 0.05). Protocol K (35.6 ± 3.2 hours) had significantly longer times to full recovery compared to P (18.2 ± 3.2 hours). Protocol K had significantly longer times to head up, crawling, and standing compared to P and PK. Cats sedated with PK (2.33 ± 0.47) required significantly more interventions for hypotension than K (0.50 ± 0.47). Protocol P (3.2 ± 0.4) and PK (1.4 ± 0.3) required significantly more interventions for bradycardia compared to K (0.8 ± 0.3). When comparing protocol K to P and PK, significant differences in blood pressure, lactate, oxygen delivery, and oxygen consumption were noted. CONCLUSIONS Cats anesthetized with P had shorter times to full recovery compared to K. Cats anesthetized with K required fewer interventions for bradycardia or hypotension but had longer recovery times compared to P or PK. Protocol PK reduced the propofol dose required to maintain optimal anesthesia.

Effect of Synthetic Colloid Administration on Coagulation in Healthy Dogs and Dogs with Systemic Inflammation

Background Synthetic colloids are often used during fluid resuscitation and affect coagulation. Objective To compare the effects of an isotonic crystalloid and synthetic colloid on coagulation in healthy dogs and dogs with systemic inflammation. Animals Sixteen adult purpose‐bred Beagles. Methods Randomized, placebo‐controlled, blinded study. Dogs were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV 0.9% NaCl or tetrastarch after administration of lipopolysaccharide or an equal volume of placebo. After a 14‐day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) but the same resuscitation fluid. Blood samples were collected at 0, 1, 2, 4, and 24 hours for measurement of coagulation variables. Results Administration of either fluid to healthy dogs and dogs with systemic inflammation resulted in similar increases in prothrombin time and activated clotting time. In comparison to saline administration, tetrastarch administration resulted in significantly decreased R (P = .017) in healthy dogs, as well as significantly increased activated partial thromboplastin time (P ≤ .016), CL30% (P ≤ .016), and K (P < .001) and significantly decreased platelet count (P = .019), α (P ≤ .001), MA (P < .001), and von Willebrand factor antigen (P < .001) and collagen binding activity (P ≤ .003) in both healthy dogs and dogs with systemic inflammation. Conclusions and Clinical Importance Tetrastarch bolus administration to dogs with systemic inflammation resulted in a transient hypocoagulability characterized by a prolonged activated partial thromboplastin time, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease.

Hypocalcemia of Critical Illness in Dogs and Cats

Hypocalcemia occurs in critically ill dogs and cats and is associated with medications, treatments, and underlying diseases such as acute kidney disease, pancreatitis, parathyroid disease, sepsis, and trauma. Possible underlying mechanisms include hypovitaminosis D, acquired or relative hypoparathyroidism, hypomagnesemia, and alterations in the ionized fraction of calcium caused by changes in chelated or protein-bound calcium. If severe or acute, hypocalcemia can cause obvious clinical signs related to muscle or neurologic hyperexcitability or more subtle signs of cardiovascular dysfunction. Emergency treatment with calcium gluconate administration is recommended when clinical signs are present or if there is moderate to severe ionized hypocalcemia.

Management of acute respiratory distress syndrome in a French Bulldog using airway pressure release ventilation

Objective To describe the successful clinical management of a dog with acute respiratory distress syndrome (ARDS) using airway pressure release ventilation (APRV). Case Summary An 18-month-old female French Bulldog was presented for routine ovariohysterectomy and correction of brachycephalic airway obstruction syndrome. Following the surgical procedures, the dog developed aspiration pneumonia and ARDS. Her clinical condition failed to improve with conventional pressure-support mechanical ventilation and she was subsequently managed with APRV. She recovered fully and exhibited no clinical or radiographic abnormalities during follow-up examinations. New or Unique Information Provided This is the first reported use of APRV to manage refractory hypoxemia associated with ARDS in a dog. This alternative mode of mechanical ventilation can be considered a feasible alternative in canine patients with ARDS.OBJECTIVE To describe the successful clinical management of a dog with acute respiratory distress syndrome (ARDS) using airway pressure release ventilation (APRV). CASE SUMMARY An 18-month-old female French Bulldog was presented for routine ovariohysterectomy and correction of brachycephalic airway obstruction syndrome. Following the surgical procedures, the dog developed aspiration pneumonia and ARDS. Her clinical condition failed to improve with conventional pressure-support mechanical ventilation and she was subsequently managed with APRV. She recovered fully and exhibited no clinical or radiographic abnormalities during follow-up examinations. NEW OR UNIQUE INFORMATION PROVIDED This is the first reported use of APRV to manage refractory hypoxemia associated with ARDS in a dog. This alternative mode of mechanical ventilation can be considered a feasible alternative in canine patients with ARDS.