Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study.

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of Escherichia coli (E. coli) following RBC transfusion in dogs with atraumatic hemorrhage. Anesthetized dogs were subject to atraumatic hemorrhage and transfusion of RBCs, then randomized to receive either deferoxamine or saline placebo of equivalent volume (n = 10 per group) in a blinded fashion. Blood was sampled before hemorrhage and then 2, 4, and 6 h later. Following hemorrhage and RBC transfusion, free iron increased in all dogs over time (both p < 0.001). Inflammation biomarkers interleukin-6 (IL6), CXC motif chemokine-8 (CXCL8), interleukin-10 (IL10), and keratinocyte-derived chemokine (KC) increased in all dogs over time (all p < 0.001). Logarithmic growth of E. coli clones within blood collected 6 h post-transfusion was not different between groups. Only total iron-binding capacity was different between groups over time, being significantly increased in the deferoxamine group at 2 and 4 h post-transfusion (both p < 0.001). In summary, while free iron and inflammation biomarkers increased post-RBC transfusion, deferoxamine administration did not impact circulating free iron, inflammation biomarkers, or in vitro growth of E. coli when compared with placebo.

Biomarkers of Coagulation and Inflammation in Dogs after Randomized Administration of 6% Hydroxyethyl Starch 130/0.4 or Hartmann's Solution.

Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES.

Thoracic Electrical Impedance Tomography-The 2022 Veterinary Consensus Statement.

Electrical impedance tomography (EIT) is a non-invasive real-time non-ionising imaging modality that has many applications. Since the first recorded use in 1978, the technology has become more widely used especially in human adult and neonatal critical care monitoring. Recently, there has been an increase in research on thoracic EIT in veterinary medicine. Real-time imaging of the thorax allows evaluation of ventilation distribution in anesthetised and conscious animals. As the technology becomes recognised in the veterinary community there is a need to standardize approaches to data collection, analysis, interpretation and nomenclature, ensuring comparison and repeatability between researchers and studies. A group of nineteen veterinarians and two biomedical engineers experienced in veterinary EIT were consulted and contributed to the preparation of this statement. The aim of this consensus is to provide an introduction to this imaging modality, to highlight clinical relevance and to include recommendations on how to effectively use thoracic EIT in veterinary species. Based on this, the consensus statement aims to address the need for a streamlined approach to veterinary thoracic EIT and includes: an introduction to the use of EIT in veterinary species, the technical background to creation of the functional images, a consensus from all contributing authors on the practical application and use of the technology, descriptions and interpretation of current available variables including appropriate statistical analysis, nomenclature recommended for consistency and future developments in thoracic EIT. The information provided in this consensus statement may benefit researchers and clinicians working within the field of veterinary thoracic EIT. We endeavor to inform future users of the benefits of this imaging modality and provide opportunities to further explore applications of this technology with regards to perfusion imaging and pathology diagnosis.

Cannula cricothyroidotomy in the impalpable neck: An observational study of simulated 'can't intubate, can't oxygenate' scenarios by teams following a cannula-first algorithm in live anaesthetised pigs.

Live animal models can be used to train anaesthetists to perform emergency front-of-neck-access. Cannula cricothyroidotomy success reported in previous wet lab studies contradicts human clinical data. This prospective, observational study reports success of a cannula-first 'can't intubate, can't oxygenate' algorithm for impalpable anatomy during high fidelity team simulations using live, anaesthetised pigs.Forty-two trained anaesthesia teams were instructed to follow the Royal Perth Hospital can't intubate, can't oxygenate algorithm to re-oxygenate a desaturating pig with impalpable neck anatomy (mean (standard deviation, SD) 16.2 (3.5) kg); mean (SD) tracheal internal diameter 11 (1.4) mm. Teams were informed that failure would prompt veterinary-led euthanasia.All teams performed percutaneous cannula cricothyroidotomy as the initial technique, with a median (interquartile range, IQR (range)) start time of 42 (35-50 (24-93)) s. First-pass percutaneous cannula success was 29% to both insufflate tracheal oxygen and re-oxygenate. Insufflation success improved with repeated percutaneous attempts (up to three), but prolonged hypoxia time increasingly necessitated euthanasia (insufflation 57%; re-oxygenation 48%). First, second and third percutaneous attempts achieved insufflation at median (IQR (range)) 74 (64-91 (46-110)) s, 111 (95-136 (79-150)) s and 141 (127-159 (122-179)) s, respectively. Eighteen teams failed with percutaneous cannulae and performed scalpel techniques, predominantly dissection cannulation (n = 17) which achieved insufflation in all cases (insufflation 100%; re-oxygenation 47%). Scalpel attempts were started at median (IQR (range)) 142 (133-218 (97-293)) s and achieved insufflation at 232 (205-303 (152-344)) s.While percutaneous cannula cricothyroidotomy could rapidly re-oxygenate, the success rate was low and teams repeated attempts beyond the recommended 60 s time frame, delaying transition to the more successful dissection cannula technique. We recommend this 'cannula-first' can't intubate, can't oxygenate algorithm adopts a 'single best effort' strategy for percutaneous cannula, with failure prompting a scalpel technique.

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs.

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.

Electrical impedance tomography to measure lung ventilation distribution in healthy horses and horses with left-sided cardiac volume overload.

BACKGROUND: Left-sided cardiac volume overload (LCVO) can cause fluid accumulation in lung tissue changing the distribution of ventilation, which can be evaluated by electrical impedance tomography (EIT). OBJECTIVES: To describe and compare EIT variables in horses with naturally occurring compensated and decompensated LCVO and compare them to a healthy cohort. ANIMALS: Fourteen adult horses, including university teaching horses and clinical cases (healthy: 8; LCVO: 4 compensated, 2 decompensated). METHODS: In this prospective cohort study, EIT was used in standing, unsedated horses and analyzed for conventional variables, ventilated right (VAR) and left (VAL) lung area, linear-plane distribution variables (avg-max VΔZLine , VΔZLine ), global peak flows, inhomogeneity factor, and estimated tidal volume. Horses with decompensated LCVO were assessed before and after administration of furosemide. Variables for healthy and LCVO-affected horses were compared using a Mann-Whitney test or unpaired t-test and observations from compensated and decompensated horses are reported. RESULTS: Compared to the healthy horses, the LCVO cohort had significantly less VAL (mean difference 3.02; 95% confidence interval .77-5.2; P = .02), more VAR (-1.13; -2.18 to -.08; P = .04), smaller avg-max VΔZLLine (2.54; 1.07-4.00; P = .003) and VΔZLLine (median difference 5.40; 1.71-9.09; P = .01). Observation of EIT alterations were reflected by clinical signs in horses with decompensated LCVO and after administration of furosemide. CONCLUSIONS AND CLINICAL IMPORTANCE: EIT measurements of ventilation distribution showed less ventilation in the left lung of horses with LCVO and might be useful as an objective assessment of the ventilation effects of cardiogenic pulmonary disease in horses.

Improved Cardiovascular Tolerance to Hemorrhage after Oral Resveratrol Pretreatment in Dogs.

Resveratrol has been shown to preserve organ function and improve survival in hemorrhagic shock rat models. This study investigated whether seven days of oral resveratrol could improve hemodynamic response to hemorrhage and confer benefits on risk of acute kidney injury (AKI) without inducing coagulopathy in a canine model. Twelve greyhound dogs were randomly allocated to receive oral resveratrol (1000 mg/day) or placebo for seven days prior to inducing hemorrhage until a targeted mean blood pressure of ≤40 mmHg was achieved. AKI biomarkers and coagulation parameters were measured before, immediately following, and two hours after hemorrhage. Dogs were euthanized, and renal tissues were examined at the end of the experiment. All investigators were blinded to the treatment allocation. A linear mixed model was used to assess effect of resveratrol on AKI biomarkers and coagulation parameters while adjusting for volume of blood loss. A significant larger volume of blood loss was required to achieve the hypotension target in the resveratrol group compared to placebo group (median 64 vs. 55 mL/kg respectively, p = 0.041). Although histological evidence of AKI was evident in all dogs, the renal tubular injury scores were not significantly different between the two groups, neither were the AKI biomarkers. Baseline (pre-hemorrhage) maximum clot firmness on the Rotational Thromboelastometry (ROTEM®) was stronger in the resveratrol group than the placebo group (median 54 vs. 43 mm respectively, p = 0.009). In summary, seven days of oral resveratrol did not appear to induce increased bleeding risk and could improve greyhound dogs' blood pressure tolerance to severe hemorrhage. Renal protective effect of resveratrol was, however, not observed.

Analytical validation and reference intervals for a commercial multiplex assay to measure five novel biomarkers for acute kidney injury in canine urine.

Novel urinary biomarkers are increasingly utilized for the diagnosis of acute kidney injury (AKI) in dogs. Magnetic-bead based immunoassays for the simultaneous measurement of multiple biomarkers represent a potentially efficient and cost effective tool for investigators; however there is limited data to support their reliable use in dogs. Analytical validation of a commercial multiplex assay for the measurement of five AKI biomarkers: clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 and neutrophil gelatinase-associated lipocalin (NGAL) in canine urine was performed. The effect of pre-analytical factors including potential interfering substances and sample storage methods were investigated. Urine from 110 healthy dogs was used to determine reference intervals for each biomarker measured, according to American Society of Veterinary Clinical Pathology guidelines. Additionally, urine from 21 dogs with pyuria was used to evaluate the impact of pyuria on biomarker concentration. The assay performed with acceptable accuracy and precision for the measurement of NGAL only. Clinically relevant urine concentrations of bilirubin, haemoglobin, and synthetic colloid solutions led to interference (mean percentage difference > +/- 15% compared to control) with measurement of all or some of the biomarkers. All biomarkers were stable in urine stored at 20-22 °C for 2 h, 4 °C for 12 h, or -20 °C for 6 months. Reference intervals could not be established for KIM-1 due to unacceptable measurement imprecision (intra- and inter assay coefficient of variation 45% and 20% respectively). Urine NGAL concentration was significantly elevated in pyuria (P < 0.001).

Prospective randomized controlled blinded clinical trial evaluating biomarkers of acute kidney injury following 6% hydroxyethyl starch 130/0.4 or Hartmann's solution in dogs.

OBJECTIVE: To evaluate the effect of 6% hydroxyethyl starch (HES) 130/0.4, compared with a Hartmann's solution control (CRYST), on urine biomarkers of acute kidney injury (AKI) in dogs prescribed a fluid bolus. DESIGN: Randomized, controlled, blinded clinical trial January 2018 to February 2019. SETTING: University teaching hospital. ANIMALS: Forty client-owned dogs. INTERVENTIONS: Dogs prescribed a fluid bolus were randomized to receive at least 10 mL/kg of HES or CRYST with clinicians and investigators blinded to fluid type. Study fluid was used for further boluses as required in the following 24 hours, to a limit of 40 mL/kg total, after which fluid administration was open-label. MEASUREMENTS AND MAIN RESULTS: Urine was collected prior to and 6, 12, and 24 hours after the first study fluid bolus. Urine concentrations of AKI biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM), clusterin, and osteopontin were measured using a magnetic bead multiplexed assay. Osmolality-indexed biomarker concentrations were compared between groups over time with linear mixed-effects models, with P < 0.05 considered significant. The mean volume of study fluid administered was not significantly different between groups (HES: 23.1 mL/kg, CRYST: 25.9 mL/kg; P = 0.47, t-test). There were no significant differences between groups in change over time of osmolality-indexed urine concentrations of NGAL (P = 0.91), cystatin C (P = 0.95), KIM (P = 0.77), clusterin (P = 0.63), or osteopontin (P = 0.91). The maximum Veterinary Acute Kidney Injury (VAKI) score up to 7 days during hospitalization (P = 1.0) and in-hospital mortality (P = 0.49) were not significantly different between groups, as compared by Fisher's exact test. CONCLUSIONS: There were no differences in change over time of urine AKI biomarkers in dogs treated with 10 - 40 mL/kg HES or CRYST over 24 hours. Larger clinical trials with patient-centered outcomes are required to investigate the safety of HES in dogs.

Comparison of pulmonary function in isoflurane anaesthetized ventilated sheep (Ovis aries) following administration of intravenous xylazine versus medetomidine.

Alpha2 receptor agonists (alpha2-agonists) are useful sedative and analgesic agents in sheep, but have adverse pulmonary effects, which are reportedly similar between different alpha2-agonists. This randomized crossover study compared pulmonary function after intravenous administration of an alpha2-agonist, either xylazine or an equipotent dose of medetomidine in 34 female sheep anaesthetized twice. Pulmonary function was assessed using spirometry, volumetric capnography, arterial blood gas analysis 1 min prior to, and 5 and 10 min after administration of the allocated alpha 2 agonist drug. Pulmonary structural changes were subsequently assessed using computed tomography (CT). Tachypnoea or hypoxaemia prompted reversal with atipamezole and exclusion of data. Data were analysed for a fixed effect of drug using a mixed effect linear model with significance set at p < 0.05. Ten sheep administered xylazine required atipamezole while none of sheep receiving medetomidine did. Xylazine produced significantly higher respiratory frequency, airway pressures, airway resistance and arterial carbon dioxide (CO2), and lower dynamic compliance, tidal volume, CO2 elimination and end tidal CO2 tension and arterial oxygen tension than medetomidine. This was associated with a significantly lower % of aerated tissue and higher % poorly and non-aerated tissue in CT images of sheep receiving xylazine versus medetomidine. In conclusion, xylazine administration produced marked decreases in pulmonary function, in ventilated isoflurane anaesthetized sheep, when compared to an equipotent dose of medetomidine when administered as an intravenous bolus supporting the use of medetomidine when alpha2-agonists are required.

Ability of different assay platforms to measure renal biomarker concentrations during ischaemia-reperfusion acute kidney injury in dogs.

Several protein biomarkers have been shown to be useful for the early diagnosis of acute kidney injury (AKI) in animals and people. Multiplex assays for measurement of a panel of renal biomarkers in canine samples have recently become available. This study compared the use of two such assays, versus previously validated ELISAs, to measure five biomarkers in canine samples during ischaemia-reperfusion (IR) AKI. Blood and urine was collected from six male anaesthetised greyhounds that underwent 1-h of renal ischaemia (severe hypotension induced by acute haemorrhage) and 2-h of reperfusion (intravenous fluid resuscitation). Histology confirmed presence of acute tubular injury at 2 h of reperfusion. Concentrations of clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1, and neutrophil gelatinase-associated lipocalin (NGAL) at baseline and following IR, measured by two different multiplex assays and previously-validated single analyte immunoassays, were compared. Only NGAL was significantly elevated following IR with all assays investigated. Whether concentrations of the other four biomarkers were significantly increased following IR depended on the assay used. Concentrations of cystatin C and KIM-1 measured with the multiplex assays were of a vast magnitude lower than those measured with the corresponding single analyte ELISAs. We conclude that further validation is required before these assays can reliably be used to measure AKI biomarkers in canine samples.

Corrigendum: Hypocoagulability and Platelet Dysfunction Are Exacerbated by Synthetic Colloids in a Canine Hemorrhagic Shock Model.

[This corrects the article DOI: 10.3389/fvets.2018.00279.].

Validation of a commercial magnetic bead-based multiplex assay for 5 novel biomarkers of acute kidney injury in canine serum.

Interest is growing in measurement of novel biomarkers for the diagnosis of acute kidney injury. Multiplex assays may provide a rapid and cost-effective way of measurement; however, sparse information is published regarding their use in dogs. We aimed to validate a commercial magnetic bead-based assay for 5 biomarkers: clusterin (Clus), cystatin C (CysC), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Intra- and inter-assay imprecision, linearity under dilution (LUD), spike recovery (S-R), and hemoglobin interference were evaluated using serum from healthy and diseased dogs. Additionally, the effect of sample type (serum vs. plasma) was investigated. All values for Clus and MCP-1 were outside the assay's measurable range. Intra- and inter-assay precision were acceptable for NGAL (CVs 8.8% and 13.2%, respectively). Regression analysis of LUD and S-R indicated good linearity for CysC and NGAL. Hemolysis did not affect measurement of any biomarker. Measured concentrations of CysC (p = 0.018) and NGAL (p = 0.015) were significantly lower in sodium citrate plasma compared to serum. We conclude that this magnetic bead-based assay is precise and accurate for NGAL measurement in canine serum. Inappropriate standards for MCP-1 and Clus, and poor accuracy for KIM-1 measurement, suggest that this assay cannot reliably quantify those biomarkers in canine blood. Measurements of CysC in canine blood using this assay must be interpreted with caution given inter-assay imprecision.

Investigation of interference from synthetic colloids on the performance of a canine neutrophil gelatinase-associated lipocalin immunoassay.

BACKGROUND: Synthetic colloid solutions, administered by rapid infusion to volume-depleted dogs, might be present in high concentrations in subsequent urine samples. The potential for these solutions to affect the performance of ELISA measurements due to sample matrix effects when studying kidney injury biomarkers requires investigation. OBJECTIVE: We aimed to investigate two different synthetic colloid solutions, 4% succinylated bovine gelatin (GEL) and 6% hydroxyethyl starch (HES), for potential interferences with a commercially available canine neutrophil gelatinase-associated lipocalin (NGAL) ELISA. METHODS: Assay interference was assessed by measuring the linearity of NGAL concentrations measured using a canine NGAL ELISA after serial dilution of a canine pooled urine sample with an assay diluent, GEL, or HES. RESULTS: NGAL recovery from urine specimens containing up to 75% HES and up to 62.5% GEL was within acceptable limits (80%-120%). NGAL recovery from the urine specimen containing 75% GEL was poor (76%). Linear regression analysis demonstrated excellent linearity under dilution when a canine urine sample was diluted with the assay diluent, GEL, or HES. CONCLUSIONS: The presence of large amounts (>62.5%) of GEL in canine urine samples could cause negative interference in the performance of the NGAL ELISA investigated.

Hydroxyethyl starch 130/0.4 (6%) and succinylated gelatine (4%) interfere with refractometry in dogs with haemorrhagic shock.

OBJECTIVE: To determine if low molecular weight synthetic colloid fluids administered to dogs interfere with refractometric estimates of total plasma protein (TPPr) and urine osmolality (UOsm). STUDY DESIGN: Experimental study. ANIMALS: Eighteen healthy Greyhound dogs. METHODS: Anaesthetized Greyhounds subjected to haemorrhage for 60 minutes were given 80 mL kg-1 of Plasma-Lyte 148 (CRYST), or 20 mL kg-1 of hydroxyethyl starch 130/0.4 (HES) or succinylated gelatine (GELO) (n = 6 per group) intravenously over 20 minutes. Refractometric (TPPr) and biuret total plasma protein (TPPb) were measured before haemorrhage (Baseline), at end of shock (Shock), immediately (T20), then 40 minutes (T60), 100 minutes (T120) and 160 minutes (T180) after fluid administration. Urine specific gravity (USG) and UOsm were measured at all time points except T20. Estimated UOsm (eUOsm) was calculated from USG. Bias and limits of agreement (LOA) for TPPr versus TPPb, and eUOsm versus UOsm were calculated at each time point. RESULTS: For dogs given CRYST and GELO, median TPPr and TPPb decreased in parallel, with a small consistent TPP bias (CRYST range of bias, 0.38-0.67 g dL-1; GELO range of bias, 0.42-0.58 g dL-1). Dogs given HES showed divergence between median TPPr and TPPb after T20, with a peak bias at T20 of 1.62 g dL-1 (LOA 1.29-1.95). Dogs given HES and GELO had markedly increased USG [HES peak median USG at T180 of 1.119 (Q1-Q3 1.103-1.122); GELO peak median USG at T120 of 1.114 (Q1-Q3 1.082-1.119)], with large increases in bias between eUOsm and UOsm [HES peak bias at T60 of 2995 mOsm kg-1 (LOA 2032-3958 mOsm kg-1); GELO peak bias at T120 of 2465 mOsm kg-1 (LOA 940-3990 mOsm kg-1)]. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of HES and GELO to dogs with haemorrhagic shock interferes with refractometric measurements for at least 3 hours after administration.

Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model.

OBJECTIVE: To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock. DESIGN: Experimental interventional study. SETTING: University. ANIMALS: Twenty-four healthy ex-racing Greyhounds. INTERVENTIONS: Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase-associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule-1 (uKIM), clusterin (uCLUST), osteopontin, gamma-glutamyl transferase, monocyte chemoattractant protein-1 (uMCP), interleukin-6, interleukin-8, protein (uPROT), hyaluronan, and F2 -isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold-change from baseline was compared between groups using mixed effects models (Bonferroni-Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test. MEASUREMENTS AND MAIN RESULTS: In dogs treated with GELO, uNGAL fold-change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between-group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable. CONCLUSION: In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES.

Hypocoagulability and Platelet Dysfunction Are Exacerbated by Synthetic Colloids in a Canine Hemorrhagic Shock Model.

Background: Hemorrhagic shock and volume replacement can alter coagulation. Synthetic colloids, hydroxyethyl starch (HES), and gelatin, may enhance hypocoagulability. Our primary objective was to describe the effect of four fluid products on coagulation in canine hemorrhagic shock. Our secondary objective was to compare measurements of coagulation during shock to baseline in all dogs. Methods: Anesthetized greyhounds subjected to atraumatic hemorrhage for 60 min were administered 20 mL kg-1 of either fresh whole blood (FWB), 6% HES 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg-1 of isotonic crystalloid over 20 min (n = 6 per group). Platelet closure time (PCT), rotational thromboelastometry (ROTEM) and plasma coagulation assays were measured at baseline, end of hemorrhage (shock), and 40 (T60), and 160 (T180) min after study fluid. ROTEM parameters included clotting time (CT), clot formation time (CFT), alpha angle, maximum clot firmness (MCF), lysis index at 60 min (LI60), and thrombodynamic potential index (TPI) for INTEM, EXTEM, FIBTEM (MCF only), and APTEM (LI60 only) profiles. Plasma coagulation assays included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration and activities of factor VII (FVII), factor VIII (FVIII), and von Willebrand Factor antigen (vWF). Between-group differences were tested using linear mixed models with post-hoc between-group comparisons (Bonferroni-Holm corrected). Differences between baseline and shock were tested using paired t-tests. Significance was set at P < 0.05. Results: GELO showed longer PCT at T60, compared with FWB and CRYST, and at T180, compared with all other groups. HES showed longer EXTEM CT at T60, compared with all other groups. HES showed lower INTEM and EXTEM MCF at T60 and lower INTEM MCF at T180, compared with FWB. Some plasma coagulation assays showed greater hypocoagulability with HES. Comparing shock to baseline, EXTEM CT, INTEM CFT, EXTEM CFT, PT, and FVIII significantly increased and PCT, INTEM CT, INTEM MCF, EXTEM MCF, EXTEM LI60, EXTEM TPI, FIBTEM MCF, APTT, fibrinogen, FVII, and vWF significantly decreased. Conclusions: In dogs with hemorrhagic shock, volume replacement with GELO caused mild platelet dysfunction and HES was associated with coagulation changes consistent with hypocoagulability, beyond effects of hemodilution. Shock alone produced some evidence of hypocoagulability.

Content validation of a Critical Appraisal Tool for Reviewing Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain.

INTRODUCTION: This article reports the content validation of a Critical Appraisal Tool designed to Review the quality of Analgesia Studies (CATRAS) involving subjects incapable of self-reporting pain and provide guidance as to the strengths and weakness of findings. The CATRAS quality items encompass 3 domains: level of evidence, methodological soundness, and grading of the pain assessment tool. OBJECTIVES: To validate a critical appraisal tool for reviewing analgesia studies involving subjects incapable of self-reporting pain. METHODS: Content validation was achieved using Delphi methodology through panel consensus. A panel of 6 experts reviewed the CATRAS in 3 rounds and quantitatively rated the relevance of the instrument and each of its quality items to their respective domains. RESULTS: Content validation was achieved for each item of the CATRAS and the tool as a whole. Item-level content validity index and kappa coefficient were at least greater than 0.83 and 0.81, respectively, for all items except for one item in domain 2 that was later removed. Scale-level content validity index was 97% (excellent content validity). CONCLUSIONS: This 67-item critical appraisal tool may enable critical and quantitative assessment of the quality of individual analgesia trials involving subjects incapable of self-reporting pain for use in systematic reviews and meta-analysis studies.

Agreement between invasive blood pressure measured centrally and peripherally in anaesthetized horses.

OBJECTIVE: To determine the agreement of invasive blood pressure measured in the facial, metatarsal and carotid arteries, and evaluate the effects of two haemodynamic conditions on agreement. STUDY DESIGN: Prospective randomized study. ANIMALS: A group of eight horses aged 7 (4-23) years with a body weight of 493 ± 33 kg. METHODS: Horses were anaesthetized and positioned in dorsal recumbency. Invasive blood pressure was measured simultaneously via catheters placed in the facial, metatarsal and carotid arteries. Cardiovascular function and agreement between arteries was assessed before and during administration of phenylephrine and sodium nitroprusside. These were administered until carotid mean pressure (MAPc) increased or decreased from baseline (65 ± 5) to >90 or <50 mmHg, respectively. Data recorded at each sample time included systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures for carotid (c), facial (f) and metatarsal (m) arteries as well as cardiac output (Q˙t) and systemic vascular resistance (SVR). Bland-Altman analysis was used to assess agreement between peripheral and central sites, and regression analysis to determine influence of Q˙t and SVR. RESULTS: The largest difference was observed in SAPc and SAPm with a bias and limits of agreement (LOA) of 2 (-15 to 19) mmHg. The bias (LOA) for MAPc and MAPf was 2 (-4 to 9) mmHg and for MAPc and MAPm was 5 (-4 to 14) mmHg. The best agreement for DAP was seen between DAPc and DAPf with bias (LOA) of 1 (-3 to 5) mmHg. Regression analysis indicated marginal influence on agreement by Q˙t on MAPc and MAPf. CONCLUSIONS AND CLINICAL RELEVANCE: MAP and DAP of the carotid artery were higher than those of the peripheral arteries, which may lead to overzealous treatment of hypotension, albeit maintaining central pressures. Q˙t and SVR did not largely influence the difference between sites.

Agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses under clinical conditions.

OBJECTIVE: To determine agreement between invasive blood pressures measured in three peripheral arteries in anaesthetized horses undergoing elective surgery. STUDY DESIGN: Prospective balanced incomplete block design. ANIMALS: A total of 18 client-owned horses. METHODS: Invasive blood pressure (IBP) was measured simultaneously in one of the following three combinations: 1) transverse facial and facial artery; 2) transverse facial and metatarsal artery; and 3) facial and metatarsal artery. The agreement in blood pressure measured for each combination was performed in six horses. At each sample time, systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures were measured concurrently in each artery, and the mean of three consecutive measurements was recorded. The position of horse, heart rate and use of dobutamine were also recorded. Bland-Altman analysis was used to assess agreement between sites. RESULTS: A total of 54 paired measurements were obtained, with 18 paired measurements from each combination. All paired measurements showed poor and haphazard (nonsystematic) agreement. The widest limit of agreement was 51 mmHg for SAP measured in the facial artery and metatarsal artery, with a bias of -11 mmHg. The smallest limit of agreement was 16 mmHg for MAP measured in the transverse facial and metatarsal artery, with a bias of 1 mmHg. CONCLUSIONS AND CLINICAL RELEVANCE: There was poor and haphazard agreement for SAP, MAP and DAP measured in each pair of peripheral arteries in this study. These results show that blood pressure measured in different peripheral arteries cannot be used interchangeably. This has implications for studies that use IBP as an outcome variable and studies determining agreement between noninvasive blood pressure and IBP measurements in horses under general anaesthesia.