A multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model.

Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters. Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature - tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured. Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters. In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.

Establishment of Reference Intervals for Caudal Vena Cava-to-Aorta Ratio Measured Ultrasonographically in Healthy Nonsedated Dogs.

The ultrasonographic assessment of the caudal vena cava-to-aorta ratio (CVC:Ao) appears to be a promising method for early recognition of alterations of intravascular volume status in veterinary medicine. The primary objective of this study was to establish the reference intervals of the CVC:Ao ratio with ultrasound in nonsedated healthy dogs. Secondary objectives were to determine the influence of the respiratory cycle and to evaluate correlations between ultrasonographic measurements, signalment and physical exam findings. Ultrasonographic measurements of Ao and CVC diameters were successfully obtained for all sixty dogs included. No evidence of a difference was observed between the measurements of Ao and CVC diameters, and CVC:Ao ratio between inspiration and expiration (P = .373, P = .318, and P = .537, respectively). The reference interval for CVC:Ao ratio (95% CI), generated from US measurements performed at any moment of the respiratory cycle was defined as 0.93 (0.91-0.95) -1.32 (1.30-1.34). The CVC:Ao ratio was significantly negatively correlated with age (r = -0.341, P = .008) and positively correlated with respiratory rate (r = 0.423, P < .001), but not with heart rate (P = .573) or arterial systolic blood pressure (P = .166). A low inter- and intraoperator variability in repeated measurements was observed for each operator and between operators. The ultrasonographic measurement of the CVC:Ao ratio appears as a simple method with low inter- and intraoperator variability using the ultrasonographic protocol described in the current study. With the reference interval established in the present study in healthy nonsedated dogs, further studies should evaluate the utility of this simple method in assessing and monitoring volume status in hypo- and hypervolemic dogs.

Use of pupillometry for the evaluation of analgesia in dogs hospitalized in intensive care: A prospective study.

A prospective study was performed on hospitalized conscious dogs. The objectives were: 1) to evaluate the feasibility and reliability of portable infrared pupillometry using a measure of photo light reflexes, 2) to identify parameters influencing measures, and 3) to compare parameters before and after the administration of analgesia. Twenty-nine dogs were included. Pupillometry was feasible by a single person. There was an excellent reliability for the evaluation of pupil diameter. There was poor to good reliability for the other parameters. There was an association between weight and mean pupil diameter (estimate = 0.1 mm, CI95 = [0.0; 0.1], P = 0.02), mean diameter variation (estimate = 0.2%, CI95 = [0.0; 0.4], P = 0.01), and mean velocity (estimate = 0.08 ms, CI95 = [0.03; 0.13], P = 0.002). Male dogs had a significantly larger mean pupil diameter than females (estimate = 1.3 mm, CI95 = [0.1; 2.5], P = 0.03). Independently of weight and sex, there was an association between mean pupil diameter and pain score: the higher the pain score, the lower the mean pupil diameter. There was a correlation between mean pupil diameter and morphine dose (ρ = -0.78, P = 0.0004). There was no significant difference in pupil diameter, velocity, and latency before and after analgesic administration. In conclusion, results do not support the use of PLR measurement by pupillometry as a pain assessment technique in hospitalized conscious dogs.

Evaluation of the impact of blood donation on tissue perfusion and sublingual microcirculation in dogs: A pilot study.

The objective was to assess the feasibility of the sublingual microcirculation evaluation in dogs by using Sidestream Dark Field (SDF) imaging device and to evaluate the impact of blood donation on sublingual microcirculation and tissue perfusion. Before and after blood sampling, macrocirculatory parameters and tissue perfusion parameters were collected. After quality assessment, four videos per individual and per period were retained for analysis. Data were presented as median (1st quartile - 3rd quartile). The evaluation of the sublingual microcirculation with SDF was feasible in sedated dogs: good quality videos could be recorded in 10/12 dogs (83%). The median blood donation volume was 14 mL/kg (13-15). A significant association between the volume of blood collected and the increase in heart rate was observed: for each milliliter of blood drawn, heart rate increased by 1 bpm (CI95% = [0.2, 2], P = 0.03). Blood collection was associated with a significant increase of shock index (estimate = 0.17, CI95% = [0.02, 0.32], P = 0.04). After blood donation, lactate concentration significantly decreased (before: 2.1 (1.7-2.8), after: 1.1 (0.8-1.7) mmol/l, P = 0.009). No significant variation of the microcirculatory parameters was observed. In conclusion, sublingual evaluation of the microcirculation with SDF technology is feasible in dogs. In the present condition, blood donation did not significantly alter microcirculation. These results need to be confirmed in a larger population.

Evaluation of pimobendan effect on sublingual microcirculation in an experimental pharmacology induced hypotension porcine model.

New therapeutic approaches are needed to simultaneously resuscitate macro- and microcirculation during circulatory shock. The aims of this study were to explore the microcirculatory and macrocirculatory effects of pimobendan, an inodilator with dual phosphodiesterase 3 inhibitor and calcium-sensitizing effects, in an experimental porcine model of pharmacologically induced hypotension associating vasoplegia and decreased cardiac output. Eight piglets were anesthetized and monitored for their hemodynamic parameters. Hypotension was induced by sevoflurane overdose until a mean arterial pressure between 40 and 45 mmHg was reached. A bolus of pimobendan (0.25 mg/kg) was administered intravenously thereafter. Sublingual microcirculation was evaluated using a Sidestream Dark Field imaging device. Hemodynamic and microcirculatory parameters were recorded at the baseline period (A), immediately before pimobendan administration (B) and after pimobendan administration (C). Induction of hypotension was associated with a decreased cardiac index and microcirculation alterations. Pimobendan administration was associated with a significant increase in heart rate, cardiac index and decrease in systemic vascular resistance index. A significant increase in proportion of perfused vessels for all vessels (+8%, [2; 14], P = 0.01) and small vessels (+8% [1; 14], P = 0.03), in microvascular flow index (+0.31 AU, [0.04; 0,58], P = 0.03) were noticed, as well as a decrease in heterogeneity index (-0.34 [-0.66; -0.03], P = 0.04) and De Backer score for all vessels (-1.04, [-1.82; -0.25], P = 0.02). In conclusion, in a simple model of pharmacologically induced hypotension, pimobendan was associated with an improvement in several microcirculatory parameters.

Performance of the Parasympathetic Tone Activity (PTA) index to predict changes in mean arterial pressure in anaesthetized horses with different health conditions.

The parasympathetic tone activity (PTA) index is based on heart rate variability and has been developed recently in animals to assess their relative parasympathetic tone. This study aimed to evaluate PTA index in anaesthetized horses with different health conditions and the performance of PTA variations (∆PTA) to predict changes in mean arterial pressure (MAP). Thirty-nine client-horses were anaesthetized for elective or colic surgery and divided into "Elective" and "Colic" groups. During anaesthesia, dobutamine was administered as treatment of hypotension (MAP <60 mmHg). In both groups, no significant variation of PTA and MAP were detected immediately before and after cutaneous incision. The PTA index increased 5 min before each hypotension, whereas it decreased 1 min after dobutamine administration. Horses of the Colic group had lower PTA values than those of the Elective group, whereas MAP did not differ between groups. To predict a 10% decrease in MAP, ΔPTA performance was associated with: AUC ROC [95% CI] =0.80 [0.73 to 0.85] (p < 0.0001), with a sensitivity of 62.5% and a specificity of 94.6% for a threshold value of 25%. The PTA index in anaesthetized horses appears to be influenced by the health condition. The shift toward lower PTA values in colic horses may reflect a sympathetic predominance. An increase in PTA of >25% in 1 min showed an acceptable performance to predict MAP decrease of >10% within 5 min. Even though these results require further evaluation, this index may thus help to predict potential autonomic dysfunctions in sick animals.

Associations between peripheral perfusion disorders, mean arterial pressure and dose of norepinephrine administrated in the early phase of septic shock.

The aim of the study was to explore the correlations between peripheral perfusion, mean arterial pressure and the dose-rate of norepinephrine (NE) infused for the treatment of septic shock. The study is retrospective analysis of data acquired prospectively on 57 patients during the first 24 hours after the occurrence of the shock. Clinical and haemodynamic characteristics, skin perfusion parameters (capillary refill time [CRT], mottling score and temperature gradients) and the dose rate of NE infusion were collected. Negative correlations between mean arterial pressure (MAP) and temperature gradients (core-to-toe: P = .03, core-to-index: P = .04) were found and abnormal CRT was associated with lower MAP (P = .02). The dose rate of NE was negatively correlated with temperature gradients (core-to-toe: P = .02, core-to-index: P = .01, forearm-to-index: P = .008) in the overall population. In patients receiving NE for at least 12 hours, the NE dose rate positively was correlated with the mottling score (P = .006), temperature gradients (core-to-toe: P = .04, forearm-to-index: P = .02, core-to-index: P = .005) and CRT (P = .001). The dose of NE administrated was associated with 14-days mortality (odds ration [OR] = 1.21 [1.06-1.38], P = .006) and with 28-days mortality (OR = 1.17 [1.01-1.36], P = 0.04). In conclusion, the study described the presence of correlations between peripheral perfusion and MAP and between peripheral perfusion and the dose rate of NE infusion.

Evaluation of the sublingual microcirculation with sidestream dark field video microscopy in horses anesthetized for an elective procedure or intestinal surgery.

OBJECTIVE: To compare the sublingual microcirculation between healthy horses anesthetized for elective procedures and horses with colic anesthetized for abdominal surgery and to determine the effect of mean arterial blood pressure (MAP) on the microcirculation. ANIMALS: 9 horses in the elective group and 8 horses in the colic group. PROCEDURES: Sublingual microcirculation was assessed with sidestream dark field video microscopy. Videos were captured at 3 time points during anesthesia. Recorded microvasculature parameters were De Backer score (DBS), total density of perfused vessels (PVD) and small vessels (PVD-S), total proportion of perfused vessels (PPV) and small vessels (PPV-S), vascular flow index (MFI), and heterogeneity index (HI). Blood pressure during hypotensive (MAP < 60 mm Hg) and normotensive (MAP ≥ 60 mm Hg) episodes was also recorded. RESULTS: During normotensive episodes, the elective group had significantly better PPV and PPV-S versus the colic group (median PPV, 76% vs 50%; median PPV-S, 73% vs 51%). In both groups, PPV decreased during anesthesia (elective group, -29%; colic group, -16%) but significantly improved in the elective group 15 minutes before the end of anesthesia (59%). During hypotensive episodes, PVD-S was better preserved in the colic group (11.1 vs 3.8 mm/mm2). No differences were identified for the microcirculatory parameters between normo- and hypotensive episodes in the colic group. CONCLUSIONS AND CLINICAL RELEVANCE: Sublingual microcirculation was better preserved in healthy horses anesthetized for elective procedures than in horses with colic anesthetized for abdominal surgery despite resuscitation maneuvers. Results indicated that the macrocirculation and microcirculation in critically ill horses may be independent.

Formula for the estimation of urine osmolality in healthy cats.

A simple and intuitive formula for the estimation of urine osmolality (Uosm) using the measured concentrations of major active urine osmolytes over a wide range of urine dilutions was proposed in healthy cats. Sixty-three urine samples were retrieved using ultrasound-guided cystocentesis from sixteen healthy cats under 5 years of age receiving intravenous infusion over a period of 24 h. Samples were collected at baseline (T0), T2, T6, T12, and T24. Urine osmolality was measured using a freezing-point osmometer, and the concentrations of osmolytes (urea, sodium, glucose, and potassium) were evaluated. A simple linear regression model for a clinical use was selected, and the agreement between the calculated and actual urine osmolalities was assessed. Urinary concentrations of urea, sodium and glucose were the three variables included in the model with the lowest AICC. Urine osmolality can be predicted accurately and precisely using urine urea, sodium and glucose with the following equation: Uosm = 1.25 × urea (mmol/l) or 20.87 × urea (g/l) + 1.1 × sodium (mmol/l) + 67 × glucose (mmol/l) or 3.72 × glucose (mg/dl). The concordance correlation coefficient for repeated measures between the actual and the calculated urine osmolality was extremely close to 1, which supported a high agreement: 0.996 (CI 95%: [0.993; 0.998]). In a population of healthy cats, urine osmolality can be predicted accurately and precisely using urinary urea, sodium and glucose concentrations. Similar formulae could potentially be established to help the clinician in pathological situations.

A new photoplethysmographic device for continuous assessment of urethral mucosa perfusion: evaluation in a porcine model.

This study proposes to evaluate an innovative device consisting of an indwelling urinary catheter equipped with a photoplethysmography (PPG) sensor in contact with the urethral mucosa that provides a continuous index called urethral perfusion index (uPI). The goal of this study was to determine if the uPI could bring out tissue perfusion modifications induced by hypotension and vasopressors in a porcine model. Twelve piglets were equipped for heart rate, MAP, cardiac index, stroke volume index, systemic vascular resistance index and uPI monitoring. The animals were exposed to different levels of mean arterial pressure (MAP), ranging from low to high values. Friedman tests with a posteriori multiple comparison were performed and a generalized linear mixed model (GLMM) was used to assess the relationship between uPI and MAP. Urethral Perfusion Index and other haemodynamic parameters varied significantly at the different time-points of interest. There was a positive correlation between MAP and uPI below a specific MAP value, called dissociation threshold (DT). Above this threshold, uPI and MAP were negatively correlated. This relationship, assessed with the GLMM, yielded a significant positive fixed effect coefficient (+ 0.2, P < 0.00001) below the DT and a significant negative fixed effect (- 0.14, P < 0.00001) above DT. In an experimental setting, the PPG device and its index uPI permitted the detection of urethral mucosa perfusion alterations associated with hypotension or excessive doses of vasopressors. Further studies are needed to evaluate this device in a clinical context.

Evaluation of microcirculation by Sidestream Dark Field imaging: Impact of hemodynamic status on the occurrence of pressure artifacts - A pilot study.

OBJECTIVE: The aims of the study were to evaluate the influence of hemodynamic status on pressure artifacts and the impact of pressure artifacts on microcirculatory flow. METHODS: Sublingual microcirculation was assessed using a Sidestream Dark Field handheld imaging device in 7 anesthetized piglets, submitted to pharmacologically-induced blood pressure variations. For each video, a pressure score of 0, 1, or 10 was assigned for the category "pressure artifacts" of the "microcirculation image quality score". Videos with a pressure score of 0 and 1 were considered as "passing videos". The videos with a score of 10 were considered as "failing videos". Multivariate logistic regression models and multivariate linear mixed models with individual random effects were used. RESULTS: As blood pressure decreased, the probability of obtaining a "failing video" increased (P = 0.0008). Pressure scores of 10 influenced significantly the perfused De Backer score (small and all vessels), the proportion of perfused vessels (small and all vessels), the microvascular flow index and the heterogeneity index. Pressure scores of 1 influenced significantly the parameters above-mentioned, except the perfused De Backer score for all vessels. CONCLUSION: The probability of obtaining pressure artifacts during recording of microcirculation videos was higher when the arterial pressure was low. The presence of acceptable pressure artifacts also influenced microcirculation analysis.

Hematological and Hemostatic Alterations Associated With a Single Extracorporeal Renal Replacement Therapy in Dogs With Acute Kidney Injury Associated Leptospirosis: A Pilot Study.

Extracorporeal renal replacement therapy (ERRT) used in dogs with acute kidney injury (AKI) may be associated with hematological and hemostatic disorders. However, its characteristics are not fully described in dogs. The purpose of this pilot study was to characterize the impact of ERRT on hematological, hemostatic, and thromboelastometric parameters in dogs with AKI. We conducted a prospective observational single cohort study in 10 client-owned dogs with AKI associated leptospirosis undergoing ERRT. Results from the CBC, coagulation tests (prothrombin and activated partial thromboplastin times [aPTT]) and rotational thromboelastometry (TEM; intrinsic TEM [inTEM] and heparinase-based TEM [hepTEM]) were recorded before and after the first ERRT session. Blood abnormalities observed before the ERRT session included thrombocytopenia (10/10), anemia (8/10), leukocytosis (4/10), prolonged aPTT (4/10) and leukopenia (1/10). After ERRT, the platelet count decreased (-25%; P = .012) whereas leukocytes (+15%; P = .046) and aPTT (+24%; P = .006) increased. The clotting time (CT) on inTEM assay and the relative variation of CT based on inTEM and hepTEM profiles increased after the ERRT session (P = .037 and P = .048, respectively). Seven dogs, 2 dogs, and 1 dog were defined as having a normal, hypocoagulable, and hypercoagulable inTEM profile after ERRT, respectively. After ERRT, no hepTEM parameter was significantly different from before treatment. Platelet count, leukocytes, aPTT and CT were altered after the first ERRT session. Beyond the hemostatic abnormalities expected by the use of UFH, thrombocytopenia appears as the only hemostatic change after a single ERRT session in dogs with AKI.

Acute kidney injury management using intermittent low efficiency haemodiafiltration in a critical care unit: 39 dogs (2012-2015).

BACKGROUND: Veterinary studies describing acute kidney injury (AKI) management using renal replacement therapy (RRT) are limited and have primarily focused on intermittent haemodialysis in North American populations. European data are lacking, although differences in populations, pathogen and toxin exposure and RRT modalities may exist between Europe and North America. The present study reviewed RRT-managed cases from the intensive care unit (ICU) of VetAgro Sup, Lyon, France, for the period 2012-2015. The aims were to describe a 4-h RRT protocol of intermittent low efficiency haemodiafiltration, population characteristics and outcomes in canine AKI cases requiring RRT and to identify prognostic variables. We defined DeltaCreat/h as the difference between the serum creatinine level after RRT treatment N and that before treatment N + 1 divided by the time between treatments (in hours). RESULTS: Thirty-nine dogs were included, and 67% were males. The median (range) age, weight, hospitalization length and number of RRT treatments were 4.4 (0.25-15) years, 26.6 (6.7-69) kg, 8 (1-23) days and 3 (1-8) treatments, respectively. The main AKI causes were leptospirosis (74.4%) and nephrotoxins (15.4%). Age (4.0 vs 5.4 years; P = 0.04), admission urine output (0.5 mL/kg/h vs 0 mL/kg/h; P = 0.02) and hospitalization length (10 vs 4 days; P < 0.001) differed between survivors and non-survivors. Hospitalization length [odds ratio (OR) = 0.4], number of treatments (OR = 5.1), serum potassium level on day 2 (OR = 1.9), DeltaCreat/h between the first and second treatments (OR = 1.2), and UOP during hospitalization (OR = 0.2) were correlated with outcome. The main causes of death were euthanasia (44%) and haemorrhagic diatheses (33%). The overall survival rate was 54%, with 55% of survivors discharged with a median creatinine < 240 µmol/L. CONCLUSIONS: This is the first description in the veterinary literature of a 4-h protocol of intermittent low efficiency haemodiafiltration to provide RRT in a veterinary critical care unit. While this protocol appears promising, the clinical application of this protocol requires further investigation. Among parameters associated with survival, UOP and DeltaCreat/h between the first and second RRT treatments may be prognostic indicators. The applicability of these parameters to other populations is unknown, and further international, multicentre prospective studies are warranted to confirm these preliminary observations.

Effects of esmolol on systemic hemodynamics and heart rate variability measured using the Analgesia/Nociception Index in resuscitated piglets with Pseudomonas aeruginosa septic shock.

OBJECTIVE: To determine the effects of esmolol on hemodynamics and heart rate variability (HRV) in the early stage of sepsis. DESIGN: Prospective, randomized, controlled, parallel trial. SETTINGS: Veterinary research laboratory. ANIMALS: Ten anesthetized piglets. INTERVENTIONS: Septic shock was induced by infusing a suspension of live Pseudomonas aeruginosa IV in 10 anesthetized piglets. The piglets were resuscitated according to a standardized protocol using Ringer's lactate solution, norepinephrine, and milrinone. Once stabilized, the piglets were randomized to receive IV esmolol, titrated to a heart rate <90/min, or control, receiving saline. A pulmonary artery catheter and an arterial catheter were inserted for hemodynamic measurements. The Analgesia/Nociception Index (ANI) and the normalized HRV frequency domain parameters - high-frequency (HF), low frequency (LF), LF/HF ratio - were recorded using a proprietary monitor. MEASUREMENTS AND MAIN RESULTS: A significant decrease in cardiac output and heart rate, and a significant increase in systemic vascular resistance were observed over time in the esmolol group in comparison to the control group. No other differences were observed in hemodynamic parameters. No significant differences were observed in ANI variations or HRV parameters over time between groups. CONCLUSIONS: The administration of esmolol produced significant changes in hemodynamics with no change in ANI values or HRV parameters. Further study is needed to understand the effect of esmolol during sepsis.

Infrared thermography: a rapid and accurate technique to detect feline aortic thromboembolism.

Objectives The objective of this study was to evaluate the diagnostic accuracy of infrared thermography in cats with acute pelvic paralysis to differentiate feline aortic thromboembolism (FATE) from non-ischaemic conditions. Methods Thermographic images were prospectively obtained at admission from cats presented for acute bilateral pelvic paralysis. Based on the final diagnosis, cats were divided into a FATE and a control group (ischaemic and non-ischaemic related pelvic paralysis, respectively). The maximum (Tmax), minimum (Tmin) and average (Tav) temperatures were determined for each of the four limbs within a hand-drawn region of interest on the dorsal limb extremity. Temperature differences between the forelimb (non-affected) and hindlimb (affected) with the highest temperature (ΔT), with the lowest temperature (δT) and from the right and left side (RightΔT and LeftΔT, respectively) were calculated. Results The FATE and control groups included 10 and six cats, respectively. In the FATE group, right hindlimb mean Tmax (23.6°C ± 1.9), left hindlimb mean Tmax (23.6°C ± 2.2) and mean Tav (22.7°C ± 2.2) were significantly lower than in the control group (26.6°C ± 3.5 [ P = 0.042]; 26.6°C ± 2.4°C [ P = 0.024] and 25.7°C ± 2.0 [ P = 0.020], respectively). ΔT, δT, RightΔT and LeftΔT were significantly higher in the FATE group than in the control group. A cut-off value of 2.4°C for RightΔTmax and LeftΔTmax allowed discrimination between the FATE and control groups with a sensitivity of 80% and 90%, respectively, a specificity of 100% for both, a positive predictive value of 100% for both, and a negative predictive value of 75% and 86%, respectively. Conclusions and relevance A minimal difference of 2.4°C between ipsilateral affected and non-affected limbs has an excellent specificity and high sensitivity for FATE diagnosis. Infrared thermography seems to be a promising, useful, easy, non-invasive and rapid method for detecting aortic thromboembolism in cats, particularly in emergency situations.

Evaluation of haemodialysis as a protective technique for preventing high daily dose amikacin nephrotoxicity: an experimental study in an ovine model.

Changes in pharmacokinetic parameters of critically ill patients make the treatment of infections challenging, particularly when multidrug-resistant bacteria are involved. The aim of this study was to evaluate the ability of haemodialysis to reduce the exposure to high dose amikacin and prevent nephrotoxicity. Amikacin 50 mg/kg was administered intravenously to six adult sheep once-daily for four days. The sheep were divided into two groups according to the implementation (group 1) or not (group 2) of haemodialysis. In group 1, haemodialysis was performed for 4 h, initiated 2 h after starting amikacin infusion. Amikacin area under the curve (AUC) and trough concentrations (Cmin) were used as markers of amikacin-induced nephrotoxicity. The median haemodialysis amikacin clearance was 2.14 L/h (35.6 mL/min), 14% of the mean total body clearance for 24 h. Haemodialysis reduced Cmin (group 1: 0.3 µg/mL [0.3-1.1]; group 2: 1.4 µg/mL [1.1-3.9]; P = 0.0003). A trend towards reduced AUC with haemodialysis was observed (group 1: 1450 µg/mL⋅h [1311-1716]; group 2: 3126 µg/mL⋅h [2581-3171]; P = 0.10). In conclusion, haemodialysis seems interesting in reducing AUC and Cmin after the injection of high-dose of amikacin, parameters known to be involved in its induced nephrotoxicity, in an experimental ovine model.

Evaluation of the Parasympathetic Tone Activity (PTA) index to assess the analgesia/nociception balance in anaesthetised dogs.

The Parasympathetic Tone Activity (PTA) is an index based on the analysis of heart rate variability that has been recently developed to assess the analgesia/nociception balance in anaesthetised animals. The present study aimed to evaluate its performance in dogs undergoing surgery. Thirty dogs admitted for elective surgeries, were anaesthetised with a standardised protocol. PTA, heart rate (HR), systolic blood pressure (SBP) and HDR (defined as an increase by >20% in HR and/or SBP within 5min) were assessed at the following predefined time-points: TStSt (steady-state, after induction of anaesthesia and before start of surgery), TClamp (clamping of surgical drapes on the skin), TCut (cutaneous incision), TPrePTA (retrospectively assessed 1min before a PTA decline of at least 20%) and TEndIso (isoflurane discontinuation). The dynamic variation of PTA over 1min (∆PTA) was calculated at each predefined time-points and its performance to predict HDR was assessed by building Receiver Operating Characteristics (ROC) curves. A significant decrease of PTA (p<0.002) was detected 1min after TClamp, TCut and TPrePTA followed by a significant increase in HR and/or SBP within 5min after the time points (p<0.01). The ΔPTA was associated with the following performance in predicting HDR: AUC ROC [95% CI]=0.80 [0.71 to 0.88] (p<0.05), with a sensitivity of 77% and a specificity of 72% for a threshold value of -18%. Although encouraging, the performance of the PTA index and its dynamic variation needs to be further evaluated, particularly in different clinical contexts.

Inhaled nitric oxide prevents NSAID-induced renal impairment in pseudo-normovolaemic piglets.

OBJECTIVE: Inhaled nitric oxide (iNO) is commonly used as a treatment of pulmonary hypertension. Its action is purported to be specific to the lung, but extrapulmonary effects have been reported. The objective of this study was to evaluate if iNO could compensate the renal impairment induced by ketoprofen, a conventional non-steroidal anti-inflammatory drug (NSAID), during general anaesthesia. METHODS: Under pseudo-normovolaemic condition, thirty piglets were randomly assigned into 5 equal groups and equipped for renal and systemic parameters measurements. A first experiment was carried out to validate methods and reproduce the renal effects of iNO (40 ppm) in comparison with a placebo (100% oxygen). In a second experiment, iNO was inhaled for 120 minutes right after NSAID treatment (ketoprofen 2 mg×kg-1 IV, and 40 ppm iNO; group KiNO) and its effects were compared to ketoprofen alone (2 mg×kg-1 IV; group K) and placebo (saline; group C). RESULTS: In this model, iNO increased significantly renal blood flow measured by ultrasonic (RBFUL: +53.2±17.2%; p = 0.008) and by PAH clearance (RBFPAH:+78.6±37.6%; p = 0.004) methods, glomerular filtration rate (GFR: +72.6±32.5%; p = 0.006) and urinary output (UO: +47.4±24.2%; p = 0.01). In the second experiment, no significant temporal variation was noted for renal parameters in groups KiNO and C, whereas a significant and constant decrease was observed in the group K for RBFUL (max -19.0±7.1%), GFR (max -26.6±10.4%) and UO (max -30.3±10.5%). CLINICAL SIGNIFICANCE: Our experiments show that iNO, released from its transport forms after its inhalation, can improve renal safety of NSAIDs. This result is promising regarding the use of NSAIDs in critical conditions, but needs to receive clinical confirmation.

Enoxaparin has no significant anticoagulation activity in healthy Beagles at a dose of 0.8 mg/kg four times daily.

Enoxaparin at 0.8 mg/kg every 6 h is used in dogs to prevent prothrombotic events, but has only been validated in healthy Greyhounds, a breed with documented hypocoagulable haemostatic profiles in vitro and bleeding tendencies in vivo. This study investigated the effects of enoxaparin at this dose rate on the coagulation parameters of eight healthy adult Beagles over a 48 h period. Anti-Xa activity was significantly increased 3 h after the second and third of nine injections, and target anti-Xa activity was only reached transiently in 3/8 dogs. Paradoxically, a transient increase in endogenous thrombin potential was observed 6 h after the third injection. Other haematologic, biochemical and coagulation parameters were not significantly altered from the baseline values during enoxaparin treatment (P > 0.05). This study suggests that assumptions regarding the pharmacodynamic effects of enoxaparin are not generalisable across breeds.