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

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

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

A comparison of the haemodynamic effects of isoflurane and halothane anaesthesia in horses

The purpose of this study was to compare the haemodynamic effects of equipotent isoflurane and halothane anaesthesia. Six adult horses were investigated on two separate occasions at least 4 weeks apart. On both occasions anaesthesia was induced by ketamine 2.2 mg/kg bwt given 5 min after i.v. administration 100 microg/kg bwt romifidine. Anaesthesia was maintained either by halothane or isoflurane (end-tidal concentrations 0.9-1.0% and 1.3-1.4%, respectively). Horses were ventilated by intermittent positive pressure to maintain PaCO2 between 40-50 mmHg. Haemodynamic variables were measured using catheter-mounted strain gauge transducers in the left and right ventricle, aorta, and right atrium. Cardiac output (CO), velocity time integral (VTI), maximal aortic blood flow velocity (Vmax) and acceleration (dv/dt(max)), left ventricular pre-ejection period (PEP) and ejection time (ET) were measured from aortic blood flow velocity waveforms obtained by transoesophageal Doppler echocardiography. Flow velocity waveforms were recorded from the femoral arteries and veins using low pulse repetition frequency Doppler ultrasound. Time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb) and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular blood flow was measured in the left and right semimembranosus muscles by laser Doppler flowmetry. Maximal rate of rise of LV pressure (LVdp/dt(max)), CO, Vmax, dv/dt(max), ET, VTI were significantly higher at all time points during isoflurane anaesthesia compared to halothane anaesthesia. Pre-ejection period and diastolic aortic blood pressure were significantly less throughout isoflurane anaesthesia compared to halothane. Isoflurane anaesthesia was associated with significantly lower systemic vascular resistance than halothane anaesthesia. Femoral arterial and venous blood flow were significantly higher and EDDS and PI were significantly lower during isoflurane anaesthesia compared to halothane anaesthesia. In addition during both halothane and isoflurane anaesthesia, femoral arterial flow was higher and EDDS and PI lower in the left (dependent) artery compared to the right (nondependent) artery. This study supports previous work demonstrating improved left ventricular systolic function during isoflurane compared to halothane anaesthesia. This improvement was still evident after premedication with a potent-long acting alpha2-adrenoreceptor agonist, romifidine, and induction of anaesthesia with ketamine. There was also evidence of increased hindlimb blood flow during isoflurane anaesthesia. However, there were differences observed in flow between the left and right hindlimb during maintenance of anaesthesia with each agent, suggesting that there were differences in regional perfusion in anaesthetised horses caused by factors unrelated to agents administere

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

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 \u3c 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 \u3c 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 \u3c 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

Doppler ultrasonography and single-fiber laser Doppler flowmetry for measurement of hind limb blood flow in anesthetized horses

OBJECTIVE: To use Doppler ultrasonography and single-fiber laser Doppler flowmetry (LDF) to evaluate blood flow in the dependent and nondependent hind limbs of anesthetized horses and to evaluate changes in femoral arterial blood flow and microvascular skeletal muscle perfusion in response to administration of phenylephrine hydrochloride or dobutamine hydrochloride. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized and positioned in left lateral recumbency. Doppler ultrasonography was used to measure velocity and volumetric flow in the femoral vessels. Single-fiber LDF was used to measure relative microvascular perfusion at a single site in the semimembranosus muscles. Phenylephrine or dobutamine was then administered to decrease or increase femoral arterial blood flow, and changes in blood flow and microvascular perfusion were recorded. RESULTS: Administration of phenylephrine resulted in significant decreases in femoral arterial and venous blood flows and cardiac output and significant increases in mean aortic blood pressure, systemic vascular resistance, and PCV. Administration of dobutamine resulted in significant increases in femoral arterial blood flow, mean aortic blood pressure, and PCV. Significant changes in microvascular perfusion were not detected. CONCLUSION AND CLINICAL RELEVANCE: Results suggest that Doppler ultrasonography and single-fiber LDF can be used to study blood flows in the hind limbs of anesthetized horses. However, further studies are required to determine why changes in femoral arterial blood flows were not associated with changes in microvascular perfusio

Effect of a 30-minute infusion of dobutamine hydrochloride on hind limb blood flow and hemodynamics in halothane-anesthetized horses

OBJECTIVE: To evaluate the hemodynamic effects of dobutamine hydrochloride (0.5 microg/kg of body weight/min) in halothane-anesthetized horses. ANIMALS: 6 adult Thoroughbred horses. PROCEDURE: Anesthesia was induced by use of romifidine (100 microg/kg) and ketamine (2.2 mg/kg), IV. Anesthesia was maintained by halothane (end-tidal concentration 0.9 to 1.0%). Aortic, left ventricular, and right atrial pressures were measured, using catheter-mounted strain gauge transducers. Cardiac output (CO), velocity time integral, maximal aortic blood flow velocity and acceleration, and left ventricular preejection period and ejection time were measured from aortic velocity waveforms obtained by transesophageal Doppler echocardiography. Velocity waveforms were recorded from the femoral vessels, using Doppler ultrasonography. The time-averaged mean velocity and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular perfusion was measured in the semimembranosus muscles by laser Doppler flowmetry. Data were recorded 60 minutes after induction of anesthesia (control) and at 15 and 30 minutes after start of an infusion of dobutamine (0.5 microg/kg/min). RESULTS: Aortic pressures were significantly increased during the infusion of dobutamine. No change was observed in the indices of left ventricular systolic function including CO. Femoral arterial flow significantly increased, and the PI and EDDS decreased. No change was observed in the femoral venous flow or in microvascular perfusion. CONCLUSIONS AND CLINICAL RELEVANCE: At this dosage, dobutamine did not alter left ventricular systolic function. Femoral blood flow was preferentially increased as the result of local vasodilatation. The lack of effect of dobutamine on microvascular perfusion suggests that increased femoral flow is not necessarily associated with improved perfusion of skeletal muscle