Lisa Smart

The effect of Hetastarch (670/0.75) in vivo on platelet closure time in the dog.

OBJECTIVE To evaluate the effect of 6% hydroxyethyl starch (HES) solution in vivo, with an average molecular weight of 670 kDa and degree of substitution of 0.75, on canine platelet function. DESIGN Prospective, controlled-experimental study. SETTING University of California, Davis, Veterinary Medical Teaching Hospital. ANIMALS Seven healthy employee-owned dogs. INTERVENTIONS Seven dogs were included in the treatment group. Four of these dogs also served as the control group. Platelet closure time (CT) was measured using a platelet function analyzer and collagen/ADP cartridges. Dogs were given 20 mL/kg of either sodium chloride 0.9% (control group, n=4) or HES (treatment group, n=7) IV over 1 hour. CT was measured before the infusion, and at 1, 3, 5, and 24 hours after the start of the infusion. MEASUREMENTS AND MAIN RESULTS There was a significant change over time from 0 to 24 hours (P<0.001), a significant difference between groups across time (P<0.001), and a significant group-by-time interaction (P=0.007). At 3 hours, mean CT for the treatment group was 122.3+/-18.1 seconds, which was significantly different (P<0.001) from the control group (71.0+/-3.5 s). At 5 hours, mean CT for the treatment group was 142.7+/-33.9 seconds, which was significantly different (P=0.001) from the control group (75.0+/-8.6 s). Mean CT at 24 hours was within the reference interval for both the control and treatment group (66.0+/-2.9 and 81.8+/-11.9 s, respectively); however, CT in 3 individual dogs in the treatment group at this time point remained prolonged. CONCLUSIONS A clinically relevant dose of HES 670/0.75 prolongs CT in dogs for up to 24 hours. This may be due to platelet dysfunction in addition to the effects of hemodilution, and therefore, may increase the risk of bleeding.

Use of intravenous lipid therapy in three cases of feline permethrin toxicosis

OBJECTIVE To describe the use of intravenous lipid emulsion (IVLE) as an adjunctive therapy in 3 cats with permethrin toxicosis. CASE SERIES SUMMARY Three cats with permethrin toxicosis were treated with IVLE in addition to the current accepted treatment regime. All 3 cats demonstrated a subjective rapid clinical improvement after the administration of IVLE, with no adverse reactions observed. NEW OR UNIQUE INFORMATION PROVIDED This is the first reported use of IVLE for feline permethrin toxicosis, with encouraging results. A possible reduction in costs associated with treatment may contribute to a reduction in euthanasia. Further investigation of the use of IVLEs in permethrin toxicosis is warranted.

Effect of hydroxyethyl starch 130/0.4 and 200/0.5 solutions on canine platelet function in vitro

OBJECTIVE To determine whether dilution of blood samples from healthy dogs with 2 hydroxyethyl starch (HES) solutions, HES 130/0.4 and HES 200/0.5, would result in platelet dysfunction as measured by closure time (Ct) beyond a dilutional effect. SAMPLE Citrated blood samples from 10 healthy dogs with a Ct within reference limits (52 to 86 seconds). PROCEDURES Blood samples were diluted 1:9 and 1:3 with 6% HES 130/0.4 and 10% HES 200/0.5 solutions and saline (0.9% NaCl) solution. Dilutions at 1:9 and 1:3 mimicked 10 mL/kg and 30 mL/kg doses, respectively, ignoring in vivo redistribution. Closure time was measured with a platelet function analyzer and compared among dilutions. RESULTS A dilutional effect on Ct was evident for the 1:3 dilution, compared with the 1:9 dilution, but only HES 200/0.5 increased the Ct beyond the dilutional effect at the 1:3 dilution, to a median Ct of 125 seconds (interquartile range, 117.5 to 139.5 seconds). No effect of HES or dilution on Ct was identified at the 1:9 dilution. CONCLUSIONS AND CLINICAL RELEVANCE 1:3 dilution of blood samples from healthy dogs with HES 200/0.5 but not HES 130/0.4 significantly increased Ct beyond the dilutional effect, suggesting that IV administration of HES 200/0.5 in dogs might cause platelet dysfunction.

The effect of hetastarch (670/0.75) on urine specific gravity and osmolality in the dog.

BACKGROUND Urine specific gravity (USG) is used clinically to estimate urine osmolality (UOsm). Although USG has been shown to have a linear correlation with UOsm in dogs, the relationship is altered when there are significant numbers of high molecular weight (MW) molecules in the urine. HYPOTHESIS USG would no longer predict UOsm in dogs given intravenous hetastarch (670/0.75)(HES). ANIMALS Eight healthy employee-owned adult dogs. METHODS Prospective, controlled experimental study. USG and UOsm were measured every 30 minutes from t=0 minutes to t=360 minutes. Dogs were administered 20 mL/kg of either NaCl 0.9% (control group, n=4) or HES (treatment group, n=8) IV over 1 hour starting at t=90 minutes. RESULTS There was a decrease in UOsm in both groups starting at t=120 minutes and continuing for the study duration, and there was no significant difference in UOsm between treatment and control groups across all time points. There was an appropriate decrease in USG from t=120 minutes for the control group. In the treatment group, USG increased significantly at t=120 minutes (P= .0006), t=150 minutes (P= .0002), and t=180 minutes (P= .0044). The largest increase in USG occurred at t=150 minutes with a mean USG of 1.070 +/- 0.021 (range 1.038-1.104). CONCLUSIONS AND CLINICAL IMPORTANCE Urine specific gravity should not be used to estimate urine solute concentration in dogs following the administration of 20 mL/kg of HES. In a clinical setting, the evaluation of USG following this dose of HES may lead to an overestimation of urine concentration.

A randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats.

OBJECTIVE To assess for any clinical benefit of intravenous lipid emulsion (ILE) for permethrin toxicosis in cats by comparing the progression of clinical signs of cats before and after treatment with ILE to cats treated with a saline control. To accomplish this objective, a clinical staging system for cats with permethrin toxicosis was developed and validated. DESIGN Prospective, multicenter, randomized, controlled clinical trial. SETTING University veterinary teaching hospital and 12 private veterinary emergency hospitals. ANIMALS Thirty-four client-owned cats with permethrin toxicosis. INTERVENTIONS A clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. The clinical staging system had 6 stages, ranging from Stage A for cats with no abnormalities to Stage F for cats with grand mal seizures. The system was validated for intraviewer and interviewer variability. Cats in the clinical trial were randomized to receive 15 mL/kg of either intravenous 0.9% saline (control) or 20% ILE over 60 minutes. For each cat, a clinical stage was recorded at set time points before and after the randomized treatment was administered. The distribution of clinical stage stratified over time was compared across treatment groups. MEASUREMENTS AND MAIN RESULTS The clinical staging system showed excellent repeatability (P = 1.0) and reliability (P = 1.0). In the clinical trial, there was a significant difference in the distribution of clinical stages over time (P < 0.001) and from presentation stage to Stage B (P = 0.006), with ILE-treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). There was no significant difference in signalment, body weight, or supportive treatment between the groups. CONCLUSIONS The clinical staging system was repeatable and reliable. Clinical stages of permethrin toxicosis in ILE-treated cats improved earlier compared to control cats, suggesting ILE may be a useful adjunctive therapy in the treatment of permethrin toxicosis in cats.

REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial

BackgroundGuidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified.Methods/designThe REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support ‘free days’ to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups.DiscussionThis is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium.Trial registrationAustralia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016.

False hyperchloraemia in a dog secondary to ingestion of horse feed supplemented with potassium bromide

BACKGROUND A dog was presented for acute abdominal distension after inadvertent access to a large amount of dry dog food and possibly horse feed consisting of chaff, pony cubes and vitamin, mineral and yeast supplements. RESULTS A marked hyperchloraemia and decreased anion gap on blood electrolyte analysis prompted a review of the patients history for potential ingestion of bromide. It was revealed that the horse feed was supplemented with potassium bromide. The serum bromide level was 23.6 mmol/L. The dog recovered uneventfully. CONCLUSION This case report highlights the importance of knowing common interferents of chemical analysis techniques.

Endothelial glycocalyx biomarkers increase in patients with infection during Emergency Department treatment

Purpose: Endothelial glycocalyx (EG) shedding may promote organ failure in sepsis. This study describes temporal changes in EG biomarkers from Emergency Department (ED) arrival, and associations with clinical characteristics. Materials and Methods: This prospective observational study included 23 patients with simple infection, 86 with sepsis and 29 healthy controls. Serum EG biomarkers included syndecan‐1, syndecan‐4 and hyaluronan. Samples were taken on enrolment in the ED (T0), 1 hour (T1), 3 hours (T3) and 12 to 24 hours (T24) later. Results: Syndecan‐1 concentration increased incrementally over time (T0‐T24, both patient groups, P < .001) whereas hyaluronan concentration peaked at T3 (T0‐T3, sepsis group, P < .001). Hyaluronan was positively associated with cumulative fluid volumes (P < .001) at T0, T1, and T3, independent of illness severity. Both syndecan‐1 (OR 1.04, 95% CI 1.01‐1.07, P = .017) and hyaluronan (OR 1.83, 95% CI 1.46‐2.30, P < .001) were associated with organ failure, independent of age and comorbidity. Syndecan‐4 concentration was not different between groups or over time. Conclusions: In contrast to previous ICU studies, EG biomarkers increased during the first 24 hours of sepsis treatment and were associated with fluid volumes and organ failure. Further investigation is required to determine if interventions delivered in the ED contribute to EG shedding.

Comparison of the use of sodium carbonate (washing soda crystals) and apomorphine for inducing emesis in dogs

OBJECTIVE To describe the use of sodium carbonate and apomorphine in a historical cohort of dogs, compare the occurrence of emesis and report any adverse effects recorded. METHODS This historical, observational study included information from medical records of dogs that received an emetic agent. The occurrence of emesis with apomorphine or sodium carbonate was calculated and the association between emesis and agent was explored, with the odds ratio and 95% confidence interval (CI) reported. A non-inferiority analysis of the occurrence of emesis for sodium carbonate was performed against an equivalence range of ±7% of the estimated occurrence of emesis with apomorphine. Owners were emailed a short survey about their dogs health after their visit to the hospital for induced emesis. RESULTS Records for 787 dogs seen from January 2007 to December 2013 were included. For apomorphine, 382/392 dogs showed emesis (97%, 95% CI 95-100%). For sodium carbonate, 320/395 dogs showed emesis (81%, 95% CI 77-85%), which fell below the equivalence range for apomorphine (97 ± 7%, 90-100%) and was considered inferior. The odds ratio of emesis with apomorphine to sodium carbonate was 9.0 (95% CI 4.6-17.6). Of 18 responses to the survey, 5 reported abnormalities after emesis (3 with sodium carbonate, 2 with apomorphine). CONCLUSION The occurrence of emesis with sodium carbonate was high but inferior to apomorphine. However, the advantages of sodium carbonate, including less expense and ease of accession compared with apomorphine, make it a viable choice in emergency medicine.

Platelet closure time in anesthetized Greyhounds with hemorrhagic shock treated with hydroxyethyl starch 130/0.4 or 0.9% sodium chloride infusions

OBJECTIVE To measure platelet closure time (PCT) in dogs during controlled hemorrhagic shock and after fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 or 0.9% sodium chloride. DESIGN Experimental interventional study. SETTING University veterinary teaching hospital. ANIMALS Eleven healthy Greyhounds. INTERVENTIONS Dogs were anesthetized and had 48 mL/kg of blood removed to induce hemorrhagic shock. Dogs received 20 mL/kg of HES 130/0.4 (n = 6) or 80 mL/kg of 0.9% sodium chloride (NaCl; n = 5) intravenously over 20 minutes. PCT was measured using the Platelet Function Analyzer-100 with collagen and adenosine-diphosphate cartridges at: T0 = 60 minutes after induction of anesthesia prior to hemorrhage, T1 = during hemorrhagic shock, and T2 = 40 minutes after completion of fluid bolus. Packed cell volume and platelet count were concurrently measured. MEASUREMENT AND MAIN RESULTS Hemorrhagic shock did not significantly change PCT, with no difference between T0 and T1. Both the HES 130/0.4 and 0.9% NaCl group had a significantly increased mean PCT at T2 of 91.4 seconds (95% CI 69.3-113.4) and 95.5 seconds (95% CI 78.2-112.8), respectively, compared to T1. The magnitude of change was significantly greater for the 0.9% NaCl group than the HES 130/0.4 group. There was no difference in the magnitude of change in PCV and platelet count between the 2 groups. The PCV and platelet count were >25% and >100,000/μL, respectively, in all dogs, except for dogs in the HES 130/0.4 group at T2 where platelet counts were <100,000/μL. CONCLUSION Controlled hemorrhagic shock in Greyhounds under anesthesia did not cause a significant change in PCT. Both HES 130/0.4 and 0.9% NaCl administration after induction of shock increased PCT. These results do not support that HES 130/0.4 causes relevant platelet dysfunction beyond hemodilution.