Effects of a single subcutaneous dose of enoxaparin on veterinary viscoelastic coagulation monitor variables in healthy cats: Double blind, placebo controlled cross-over trial.

BACKGROUND: Cats placed on anticoagulant medication require frequent monitoring. The veterinary viscoelastic coagulation monitor (VCM-Vet) could provide a convenient and cost-effective monitoring, enabling therapeutic decision making. HYPOTHESIS/OBJECTIVES: Enoxaparin will lead to changes in VCM-Vet variables and these will correlate with antiXa activity. ANIMALS: Twenty-one healthy cats. METHODS: Cats were randomized to receive either enoxaparin (1 mg/kg) subcutaneously or 0.9% NaCl (equal volume) and crossed over with a 7-day washout period. The investigators were blinded to group allocation until data analysis. Jugular blood samples were drawn at time 0, and 2, 4, and 8 hours after injection for VCM-Vet analysis within 2 min of collection. Citrated plasma was frozen at -80°C for antiXa activity analysis. A Generalized Linear Model was completed to assess changes between baseline measurements and all time points. RESULTS: Significant differences between the enoxaparin-treated cats and controls at for T0h and T2h were found and presented as mean ± SD for clotting time (enoxaparin, 593.4 ± 78.0 s; control, 448.5 ± 50.3 s, P < .001), clot formation time (enoxaparin, 183.1 ± 41.7 s; control, 155.4 ± 28.0 s, P = .001), and alpha angle (enoxaparin, 52.4 ± 6.1°; control, 56.9 ± 3.7 s, P = .003). AntiXa activity was significantly different between T0 and all other timepoints for the enoxaparin group (P < .001). There was no correlation between changes in clotting time and antiXa activity. CONCLUSIONS AND CLINICAL IMPORTANCE: The VCM-Vet detects a difference at 2 hours after single-dose enoxaparin administration and it can be useful for anticoagulant therapy monitoring in cats.

Clinical parameters at time of admission as prognostic indicators in cats presented for trauma to an emergency centre in New Zealand: a retrospective analysis.

OBJECTIVES: The aims of this study were to describe the clinical features of cats presented for trauma in a first-opinion and referral teaching hospital in New Zealand, and to determine the relationship between those features and outcome. METHODS: The electronic medical records of cats presented for trauma to the Massey University Pet Emergency Centre between September 2013 and January 2019 were examined, from which the signalment, clinical parameters and patient outcomes were extracted. Cases were assigned an Animal Trauma Triage (ATT) score and Modified Glasgow Coma Scale (MGCS) score. Variables were selected for inclusion in a logistic regression model to predict survival, and backward elimination was used to find the minimal significant model. RESULTS: In total, 530 cats met the inclusion criteria. The cause of injury was not known in the majority of cases (38.0%). The most common location of injury was the hindlimbs/pelvis/tail (n = 247; 41%), and skin lacerations/abrasions were the most common specific injury. Multivariate analysis revealed altered mentation (odds ratio [OR] 0.31, P = 0.029), hypothermia (rectal temperature <37.8°C [<100.04°F]; OR 0.45, P = 0.015) and an ATT score ⩾5 (OR 0.13, P <0.001) to be statistically significantly associated with mortality. CONCLUSIONS AND RELEVANCE: Altered mentation and hypothermia are easily measurable perfusion parameter abnormalities associated with mortality in cats presenting with trauma. The ATT score appears to be an accurate prognostic indicator in cats presenting with trauma in New Zealand. These results highlight the importance of incorporating a hands-on triage examination in each cat that presents as an emergency after trauma.

Ultrasonographically derived caudal vena cava parameters acquired in a standing position and lateral recumbency in healthy, lightly sedated cats: a pilot study.

OBJECTIVES: The aim of this study was to determine the feasibility of ultrasonographically measuring the caudal vena cava (CVC) at the subxiphoid view of healthy, lightly sedated cats in a standing position and lateral recumbency. METHODS: This was a prospective, observational, experimental single-centre study. Twenty healthy research-purposed cats were enrolled. Two trained operators scanned each cat in two positions - standing and lateral recumbency - in a randomised order. CVC diameter was measured at the narrowest diameter during inspiration and at the widest diameter during expiration, at two anatomical locations along the CVC - where the CVC crosses the diaphragm (base) and 2 mm caudal to the diaphragm. The CVC collapsibility index (CVC-CI) was calculated for each site. Normalcy was assessed with a Shapiro-Wilk test. A one-way ANOVA with post-hoc Tukey's test was used to compare inspiratory with expiratory values within and between groups. A paired t-test compared the CVC-CI between groups (P ⩽0.05 indicated statistical significance). Spearman's correlation and Bland-Altman analysis assessed inter-operator variability. RESULTS: All ultrasonographic data passed normalcy and were reported as mean ± SD. When compared with each other, inspiratory and expiratory values were statistically different for position, location and operator (all P <0.0001). There was no statistically significant difference between lateral recumbency or standing position for inspiratory, expiratory and CVC-CI values. Inter-operator variability was substantial, with operator 2 consistently obtaining smaller measurements than operator 1. The mean CVC-CI in lateral recumbency at the base was 24% for operator 1 and 37% for operator 2. For the same site in standing position, CVC-CI was 27% and 41% for operators 1 and 2, respectively. CONCLUSIONS AND RELEVANCE: This pilot study demonstrates that it is possible to ultrasonographically measure the CVC diameter in both lateral recumbency and a standing position in healthy, lightly sedated cats. However, measurements obtained are operator dependent with variability between individuals. Further studies are needed to determine if ultrasonographic CVC assessment will prove helpful in estimating intravascular volume status in cats.

Colloids Yes or No? - a "Gretchen Question" Answered.

Colloid solutions, both natural and synthetic, had been widely accepted as having superior volume expanding effects than crystalloids. Synthetic colloid solutions were previously considered at least as effective as natural colloids, as well as being cheaper and easily available. As a result, synthetic colloids (and HES in particular) were the preferred resuscitation fluid in many countries. In the past decade, several cascading events have called into question their efficacy and revealed their harmful effects. In 2013, the medicines authorities placed substantial restrictions on HES administration in people which has resulted in an overall decrease in their use. Whether natural colloids (such as albumin-containing solutions) should replace synthetic colloids remains inconclusive based on the current evidence. Albumin seems to be safer than synthetic colloids in people, but clear evidence of a positive effect on survival is still lacking. Furthermore, species-specific albumin is not widely available, while xenotransfusions with human serum albumin have known side effects. Veterinary data on the safety and efficacy of synthetic and natural colloids is limited to mostly retrospective evaluations or experimental studies with small numbers of patients (mainly dogs). Large, prospective, randomized, long-term outcome-oriented studies are lacking. This review focuses on advantages and disadvantages of synthetic and natural colloids in veterinary medicine. Adopting human guidelines is weighed against the particularities of our specific patient populations, including the risk-benefit ratio and lack of alternatives available in human medicine.

Rapid Patient-Side Evaluation of Endothelial Glycocalyx Thickness in Healthy Sedated Cats Using GlycoCheck® Software.

The endothelial glycocalyx (EG) determines transvascular fluid fluxes, and influences inflammation, coagulation, and capillary blood flow. The GlycoCheck® software calculates EG thickness using sidestream dark field videomicroscopy recordings. This method has not been evaluated for use in cats. The aim of the present study was to evaluate the use of GlycoCheck® for estimating EG thickness in healthy cats, and to investigate the variability of EG thickness in this population. One hundred and one healthy research-purposed cats were included in the study. The cats were sedated, and a handheld videomicroscope, connected to GlycoCheck® software, was used to evaluate the sublingual microvasculature. The parameters measured included perfused boundary region (PBR, an indirect measurement of EG thickness) in vessels between 5 and 25 µm in diameter, valid vessel density, percentage red blood cell filling, and median red blood cell column width. Heart rate, respiratory rate, pulse oximetry and oscillometric blood pressure readings were also recorded. There were 35 neutered male cats, 11 intact males, 38 neutered females, and 17 intact females. The average age was 63 months (range, 11-160 months). Tolerance intervals for PBR (vessel diameter 5-25 µm) were 1.89-3.00 µm (95% CI, lower limit 1.76-2.04, upper limit 2.83-3.13 µm); for valid vessel density were 73.33-333.33 µm/mm2 (95% CI, lower limit 77.00-99.33, upper limit 312.67-350.33 µm/mm2); for percentage red blood cell filling were 59.85-85.07% (95% CI, lower limit 58.97-63.33, upper limit 83.07-88.20 %); and for median red blood cell column width were 5.63-8.59 µm (95% CI, lower limit 5.28-6.07, upper limit 8.14-9.51 µm). There was a negative association between median red blood cell column width and body weight (p = 0.007). The median red blood cell column was significantly wider in intact females when compared to spayed females (p = 0.033). The GlycoCheck® analysis was easily performed in healthy sedated cats. Clinical variables did not have an effect on the EG thickness. These results suggest that this technique could be valuable for evaluation of the EG and microvascular parameters in cats.

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on electrolyte and acid-base variables in dogs with suspected intracranial hypertension.

BACKGROUND: Hyperosmolar agents frequently are used to decrease intracranial pressure but their effects on electrolyte and acid-base variables have not been prospectively investigated. OBJECTIVES: Compare duration and magnitude of changes in electrolyte and acid-base variables after hyperosmolar treatment. ANIMALS: Twenty-eight client-owned dogs with intracranial hypertension caused by various pathologies. METHODS: Prospective, randomized, nonblinded, experimental cohort study. Fifteen dogs received a single dose (4 mL/kg) of 7.2% hypertonic saline (HTS), 13 dogs received 20% mannitol (MAN) 1 g/kg IV. Electrolyte and acid-base variables were measured before (T0 ), and 5 (T5 ), 60 (T60 ), and 120 (T120 ) minutes after administration. Variables were compared between treatments and among time points within treatment groups. RESULTS: Mean plasma sodium and chloride concentrations were higher after HTS than MAN at T5 (158 vs 141 mEq/L; 126 vs 109 mEq/L) and significant differences were maintained at all time points. After HTS, plasma sodium and chloride concentrations remained increased from T0 at all time points. After MAN, plasma sodium and chloride concentrations decreased at T5 , but these changes were not maintained at T60 and T120 . Plasma potassium concentration was lower at T5 after HTS compared with T0 (3.6 vs 3.9 mEq/L) and compared to MAN (3.6 vs 4.1 mEq/L). At T60 and T120 , plasma ionized calcium concentration was lower after HTS than MAN (1.2 vs 1.3 mmol/L). No significant differences were found in acid-base variables between treatments. CONCLUSIONS AND CLINICAL IMPORTANCE: At the administered dose, dogs receiving HTS showed sustained increases in plasma sodium and chloride concentrations, whereas dogs receiving MAN showed transient decreases. Future studies should assess the effects of multiple doses of hyperosmolar agents on electrolyte and acid-base variables.

Starch Wars-New Episodes of the Saga. Changes in Regulations on Hydroxyethyl Starch in the European Union.

After a safety review of hydroxyethyl starch (HES) solutions in 2013, restrictions on the use of HES were introduced in the European Union (EU) to reduce the risk of kidney injury and death in certain patient populations. Similar restrictions were introduced by the Food and Drug Administration in the United States and other countries. In October 2017, a second safety review of HES solutions was triggered by the European pharmacovigilance authorities based on a request by the Swedish Medical Products Agency to completely suspend HES. After several meetings and repeated evaluations, the recommendation to ban HES was ultimately not endorsed by the responsible committee; however, there was a vote for more restricted access to the drug and rigorous monitoring of policy adherence. This review delineates developments in the European pharmacovigilance risk assessment of HES solutions between 2013 and 2018. In addition, the divergent experts' opinions and the controversy surrounding this official assessment are described. As the new decisions might influence the availability of HES products for veterinary patients, potential alternatives to HES solutions, such as albumin solutions and gelatin, are briefly discussed.

Current Trends in Volume Replacement Therapy and the Use of Synthetic Colloids in Small Animals-An Internet-Based Survey (2016).

The use of synthetic colloids (SCs), particularly hydroxyethyl starch (HES), in people has changed in recent years following new evidence raising concerns about their efficacy and safety. Although fluid therapy guidelines for small animals are often extrapolated from human medicine, little information exists on current practice in veterinary medicine. The objective of the present study was to investigate current fluid selection, use of plasma volume expanders including SCs, and recent changes in their use in small animal practice. An Internet-based survey was conducted, inviting veterinarians to report their practices in fluid resuscitation and colloid osmotic pressure support, their choice of SC, and perceived adverse effects and contraindications associated with SC use. There were 1,134 respondents from 42 countries, including 46% general practitioners and 38% diplomates. Isotonic crystalloids, HES, and hypertonic saline were chosen by most respondents for fluid resuscitation, and HES by 75% of respondents for colloid osmotic support. Dextran and gelatin were used by some European respondents. Human serum albumin was used more than canine albumin but 45% of respondents, particularly those from Australia and New Zealand, used no albumin product. The majority (70%) of respondents changed their practice regarding SCs in recent years (mostly by limiting their use), largely due to safety concerns. However, only 27% of respondents worked in an institution that had a general policy on SC use. Impaired renal function, coagulopathy, and hypertension were most often considered contraindications; impaired coagulation tests and increased respiratory rate were the most frequently perceived adverse effects. The use of HES remains widespread practice in small animals, regardless of geographic location. Nevertheless, awareness of safety issues and restrictions on the use of SCs imposed in human medicine seems to have prompted a decrease in use of SCs by veterinarians. Given the paucity of evidence regarding efficacy and safety, and differences in cohorts between human and veterinary critical care patients, studies are needed to establish evidence-based guidelines specific for dogs and cats.

Hydrocortisone therapy in a cat with vasopressor-refractory septic shock and suspected critical illness-related corticosteroid insufficiency.

A 27-month-old female cat was presented with septic peritonitis secondary to a ruptured pyometra and subsequent pyothorax. Vasopressor-refractory septic shock led to a suspicion of critical illness-related corticosteroid insufficiency, successfully treated with intravenous hydrocortisone. Previous megestrol acetate administration may have played a role in the development of adrenocortical dysfunction.

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study.

BACKGROUND: Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T0), as well as 5 (T5), 60 (T60) and 120 (T120) minutes after administration of HTS or mannitol. Data at T5, T60 and T120 were analyzed as a percentage of values at T0 for comparison between groups, and as absolute values for comparison between time points, respectively. RESULTS: No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T5 (both groups) and T60 (HTS group). CONCLUSIONS: Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

Effect of tetrastarch (hydroxyethyl starch 130/0.4) on plasma creatinine concentration in cats: a retrospective analysis (2010-2015).

Objectives The objective was to determine survival and changes in creatinine concentrations after administration of 6% tetrastarch (hydroxyethyl starch [HES] 130/0.4) vs crystalloids in critically ill cats. Methods The medical records were reviewed for cats admitted to the intensive care unit with at least two plasma creatinine measurements and initial concentrations not exceeding the upper reference interval. Cats were excluded if they had received HES prior to admission or if they had received fluid therapy for <24 h between initial and subsequent measurements. Changes in creatinine concentrations were evaluated as the percentage change from initial values to the maximum subsequent measurements. Cats receiving only crystalloids were assigned to the crystalloid group; cats receiving only HES or HES and crystalloids were assigned to the HES group. Results Ninety-three cats were included in the study (62 in the crystalloid group, 31 in the HES group). The total median cumulative HES dose was 94 ml/kg (range 26-422 ml/kg) and 24 ml/kg/day (range 16-42 ml/kg/day). No difference was detected between the groups for age, sex, body weight or mortality. The HES group had a significantly longer length of hospitalisation ( P = 0.012), lower albumin concentrations ( P <0.001), higher Acute Patient Physiologic and Laboratory Evaluation scores ( P = 0.037) and higher incidence of systemic inflammatory response syndrome ( P = 0.009) and sepsis ( P = 0.013). There was no significant difference in initial, maximum or maximum change in creatinine concentrations between the groups. Moreover, there was no significant difference in maximum change in creatinine concentrations in the subgroups of cats with systemic inflammatory response syndrome or sepsis. Conclusions and relevance In this population of cats, the administration of HES did not result in a significantly greater increase in creatinine from values measured on admission or higher mortality compared with administration of crystalloids. Further prospective studies are needed to assess both safety and efficacy of HES in cats before recommendations can be made.

Retrospective evaluation of the effects of administration of tetrastarch (hydroxyethyl starch 130/0.4) on plasma creatinine concentration in dogs (2010-2013): 201 dogs.

OBJECTIVE: To determine changes in creatinine concentrations following the administration of 6% tetrastarch (hydroxyethyl starch [HES] 130/0.4) compared to crystalloids (CRYSs) in critically ill dogs. DESIGN: Retrospective case series (2010-2013). SETTING: University teaching hospital. ANIMALS: Two hundred and one dogs admitted to the intensive care unit with initial plasma creatinine concentrations not exceeding laboratory reference intervals (52-117 µmol/L [0.6-1.3 mg/dL]) and receiving either CRYSs alone (CRYS group, n = 115) or HES with or without CRYSs (HES group, n = 86) for at least 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Creatinine concentrations at admission to the intensive care unit (T0), and 2-13 days (T1) and 2-12 weeks (T2) after initiation of fluid therapy were analyzed. Creatinine concentrations were analyzed as absolute values and as the maximum percentage change from T0 to T1 (T1max%) and from T0 to T2 (T2max%), respectively. Creatinine concentrations were available for 192 dogs during T1 and 37 dogs during T2. The median cumulative dose of HES was 86 mL/kg (range, 12-336 mL/kg). No difference was detected between the groups for age, gender, body weight, and length of hospitalization. Outcome was significantly different between the HES (66% survived) and the CRYS (87% survived) groups (P = 0.014). No significant difference was detected between groups for creatinine concentrations at T0, T1, T2, T1max%, or T2max%. No significant difference was detected between the groups for T1max% creatinine in dogs subclassified as having systemic inflammatory response syndrome or sepsis. CONCLUSIONS: HES administration in this canine population did not result in increased creatinine concentrations compared to administration of CRYSs. Further studies are needed to establish the safety of HES in critically ill dogs.

Controversies in the use of hydroxyethyl starch solutions in small animal emergency and critical care.

OBJECTIVES: To (1) review the development and medical applications of hydroxyethyl starch (HES) solutions with particular emphasis on its physiochemical properties; (2) critically appraise the available evidence in human and veterinary medicine, and (3) evaluate the potential risks and benefits associated with their use in critically ill small animals. DATA SOURCES: Human and veterinary original research articles, scientific reviews, and textbook sources from 1950 to the present. HUMAN DATA SYNTHESIS: HES solutions have been used extensively in people for over 30 years and ever since its introduction there has been a great deal of debate over its safety and efficacy. Recently, results of seminal trials and meta-analyses showing increased risks related to kidney dysfunction and mortality in septic and critically ill patients, have led to the restriction of HES use in these patient populations by European regulatory authorities. Although the initial ban on the use of HES in Europe has been eased, proof regarding the benefits and safety profile of HES in trauma and surgical patient populations has been requested by these same European regulatory authorities. VETERINARY DATA SYNTHESIS: The veterinary literature is limited mostly to experimental studies and clinical investigations with small populations of patients with short-term end points and there is insufficient evidence to generate recommendations. CONCLUSIONS: Currently, there are no consensus recommendations regarding the use of HES in veterinary medicine. Veterinarians and institutions affected by the HES restrictions have had to critically reassess the risks and benefits related to HES usage based on the available information and sometimes adapt their procedures and policies based on their reassessment. Meanwhile, large, prospective, randomized veterinary studies evaluating HES use are needed to achieve relevant levels of evidence to enable formulation of specific veterinary guidelines.