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The primary goals of positive end-expiratory pressure (PEEP) are to restore functional residual capacity through recruitment and prevention of alveolar collapse. Through these mechanisms, PEEP improves arterial oxygenation and may reduce the risk of ventilator-induced lung injury (VILI). Because of the many potential negative effects associated with the use of PEEP, much research has concentrated on determining the optimal PEEP setting. Arterial oxygenation targets and pressure-volume loops have been utilized to set the optimal PEEP for decades. Several other techniques have been suggested, including the use of PEEP tables, compliance, driving pressure (DP), stress index (SI), transpulmonary pressures, imaging, and electrical impedance tomography. Each of these techniques has its own benefits and limitations and there is currently not one technique that is recommended above all others.

Abstract Background Grape-induced acute kidney injury (AKI) is caused by tartaric acid and may lead to death in dogs. Probenecid, an organic anion transporter-1 inhibitor, recently has been shown to block the uptake of tartaric acid in Madin–Darby canine kidney cells and has been suggested as a possible target for prevention of AKI after grape ingestion. Hypothesis/Aims Assess the safety and pharmacokinetics (PK) of PO probenecid in dogs. We hypothesized that probenecid would result in mild, self-limiting gastrointestinal (GI) adverse effects and would be safe in healthy dogs. Additionally, we hypothesized that PO probenecid (50 mg/kg) would have adequate bioavailability and achieve pharmacologically active plasma drug concentrations. Animals Six healthy beagle dogs. Methods Pharmacokinetic (PK) study. Dogs were given 50 mg/kg of probenecid PO, with PK data collected for 48 h after administration. Complete blood count, serum biochemistry profile, urinalysis, and clinical monitoring were performed throughout a 21-day study period to assess safety. Plasma concentration versus time data was analyzed using non-compartmental and two-compartmental modeling. Results Orally administered probenecid had excellent estimated bioavailability (82.6%) and rapid absorption, with a mean maximal plasma concentration of 589.3 μM (range: 368.0–830.5 μM) within 1.5 h. The mean volume of distribution was 0.71 L/kg, with mean systemic clearance of 0.022 L/h/kg and mean half-life of 24.1 h. Probenecid was well tolerated by all six dogs, with no clinically relevant adverse effects noted. Conclusions and Clinical Importance Orally administered probenecid is safe and bioavailable in healthy dogs. Future clinical trials assessing PO probenecid in dogs with known tartaric acid ingestion are warranted.

Accurate assessment of intravascular volume is critical for precise fluid prescription. In people, bedside or point of care ultrasound is used to measure the inferior vena cava, with or without paired aortic measurement, to estimate intravascular volume. To determine if point of care ultrasound measurement of the caudal vena cava (CVC) diameter or the CVC diameter to the abdominal aorta (Ao) diameter (CVC:Ao) at the paralumbar view are associated with changes in intravascular volume, mean arterial pressure (MAP), or cardiac output in normovolemic and hypovolemic dogs. 8 purpose-bred dogs. Pressure-targeted hemorrhagic shock was induced in purpose-bred dogs under general anesthesia. Dogs were exsanguinated to a mean arterial pressure of 40 mmHg, or a maximum 60% blood volume lost, then auto-transfused shed blood. At a left paralumbar view, longitudinal plane measurements of the abdominal CVC diameter and aortic diameter were obtained. Measurements were performed at 4 timepoints: baseline under anesthesia (TP1), after hemorrhagic shock was induced (TP2), after ½ of shed blood had been re-transfused (TP3), and post-resuscitation with completed re-transfusion (TP4). Additional variables collected included cardiac output using thermodilution and arterial blood pressure. CVC:Ao was not significantly different between timepoints and was not associated with changes in CO (  = 0.28) or MAP (  = 0.50). CVC diameter was significantly different between baseline (TP1) and hemorrhagic shock (TP2). CVC diameter was significantly different at TP2 compared to TP1 after controlling for the effect of CO (  = 0.03) and MAP (  = 0.001). Aortic diameter was also significantly different at TP2 (  = 0.002, p = 0.001) and TP3 (  = 0.023,  = 0.017) compared to TP1 after controlling for CO and MAP. Obtaining point of care ultrasound images for CVC:Ao measurement was feasible. With a marked decrease in intravascular volume, both CVC and Ao diameter decreased, resulting in an unchanged CVC:Ao. Despite changes in CVC and Ao diameters, these changes were not associated with measured changes in CO, emphasizing that CO is not a direct estimate of intravascular volume and is affected by many compensatory mechanisms. Additional studies are needed to determine the most accurate method for bedside measurement of intravascular volume status.

The purpose of this study was to evaluate plasma ondansetron (OND) concentrations in a population of dogs with naturally occurring nausea after oral OND administration. Twenty-four dogs were randomly assigned to receive one of the following doses of oral OND: 0.5 mg/kg q8h, 0.5 mg/kg q12h, 1 mg/kg q8h, or 1 mg/kg q12h. Blood samples for plasma OND measurements were collected at baseline and 2, 4, and 8 h after administration of the first dose of OND. OND concentrations averaged over an 8 h time period were not significantly different between dose groups (0.5 mg/kg group: median 8.5 ng/mL [range 1–96.8 ng/mL], 1 mg/kg group: median 7.4 ng/mL [range 1–278.7 ng/mL]). The mean maximum concentrations in the 0.5 mg/kg and 1 mg/kg groups were 35.8 ± 49.0 ng/mL and 63.3 ± 121.1 ng/mL, respectively. OND concentrations were below the lower limit of quantification (LLOQ) in 50% (18/36) of samples in the 0.5 mg/kg groups and 39% (14/36) of samples in the 1 mg/kg groups. Six dogs (6/24, 25%) did not have OND detected at any time. The mean nausea scores at baseline were similar amongst all groups and decreased over time. The bioavailability of oral OND appears to be poor. Despite low plasma OND concentrations, nausea scores improved over time.

IntroductionTo evaluate microcirculation and endothelial glycocalyx (eGC) variables using sidestream darkfield (SDF) videomicroscopy in canine cardiopulmonary bypass (CPB).MethodsDogs undergoing CPB for surgical correction of naturally-occurring cardiac disease were prospectively included. Variables collected included patient demographics, underlying cardiac disease, red blood cell flow (Flow), 4-25 μm vessel density (Density), absolute capillary blood volume (CBVabs), relative capillary blood volume (CBVrel) and eGC width assessed by perfused boundary region (PBR). Anesthetized healthy dogs were used as control. Microcirculation and eGC variables were compared at baseline under anesthesia (T0), on CPB prior to cross clamping (T1), after cross clamp removal following surgical correction (T2) and at surgical closure (T3).ResultsTwelve dogs were enrolled, including 10 with a complete dataset. Median Flow was 233.9, 79.9, 164.3, and 136.1 μm/s at T0, T1, T2, and T3, respectively, ( p  = 1.00). Median Density was 173.3, 118.4, 121.0 and 155.4 mm/mm2 at T0, T1, T2, and T3, respectively, ( p  = 1.00). Median CBVabs decreased over time: 7.4, 6.6, 4.8 and 4.7 103μm3 at T0, T1, T2, and T3, respectively, ( p  < 0.01). Median CBVrel increased over time: 1.1, 1.5,1.1, and 1.3 103μm3 at T0, T1, T2, and T3, respectively, ( p  < 0.001). Median PBR increased over time: 1.8, 2.1, 2.4, 2.1 μm at T0, T1, T2, and T3, respectively, ( p  < 0.001). Compared to control dogs ( n  = 8), CPB dogs had lower CBVabs at T0.ConclusionAlterations in eGC thickness and microvascular occur in dogs undergoing CPB for naturally-occurring cardiac disease.