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.

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.

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.

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 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.

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.

Effectiveness of chest physiotherapy using passive slow expiratory techniques in dogs with airway fluid accumulation: A randomized controlled trial.

BACKGROUND: Prolonged slow expiration (PSE) and assisted cough (AC) are airway clearance techniques feasible and well tolerated in dogs. OBJECTIVES: To evaluate the effectiveness of PSE and AC as chest physiotherapy (CP) techniques in dogs with airway fluid accumulation. ANIMALS: Thirty-one client-owned dogs hospitalized in an intensive care unit from October 2014 to May 2018. METHODS: Prospective randomized controlled trial. Dogs presented with or developing acute dyspnea during hospitalization associated with airway fluid accumulation were assigned to CP group (medical treatment and CP, 15 dogs) or control group (medical treatment alone, 16 dogs). The arterial partial pressure of oxygen (PaO2 ) to fraction of inspired oxygen (FiO2 ) ratio (P/F ratio; PaO2 /FiO2 × 100) was calculated daily for the 1st 48 hours of hospitalization and using the last arterial blood gas performed before discharge or death. The ratio of days of hospitalization with oxygen/total number of hospitalization days (ratio of oxygen-free-days [O2 Free]) was calculated. RESULTS: During the 1st 48 hours, the P/F ratio increased significantly in the CP group compared to the control group (+ 35.1 mm Hg/day; 95% confidence interval [CI] = 0.4-57.5; P = .03). The (median; 1st quartile to 3rd quartile) difference between the P/F ratio at discharge and inclusion was significantly higher in the CP group (178 mm Hg; 123-241) than in the control group (54 mm Hg; -19 - 109; P = .001). Mean O2 Free increased by 46.4% in the CP group compared with control group (95% CI = 16-59; P = .001). Mortality was 13% (2/15) in the CP group and 44% (7/16) in the control group (P = .07). CONCLUSIONS AND CLINICAL IMPORTANCE: Prolonged slow expiration and AC improved P/F ratio within 48 hours and decreased need for oxygenation in dyspneic dogs with acute airway fluid accumulation.

Core-to-skin temperature gradient measured by thermography predicts day-8 mortality in septic shock: A prospective observational study.

BACKGROUND: Septic shock is associated with altered peripheral perfusion. Core-to-skin temperature gradient depends on skin perfusion and microcirculatory function. We hypothesized that a high core-to-skin temperature gradient is correlated with mortality in septic shock. METHODS: We conducted a prospective observational study including 61 patients at the first 24 h of a septic shock in an intensive care unit. During the 24 first hours after norepinephrine administration, we collected clinical and circulatory characteristics, skin perfusion assessment (Capillary refill time (CRT), Mottling score) and we measured skin temperature with an infrared thermographic camera. We measured the Core-to-skin temperature gradient to evaluate if it is a predictor of day-8 mortality. RESULTS: Day-8 mortality was 16.3%. Core-to-index finger temperature gradient >7 °C was associated with day-8 mortality (OR = 18.0, [3.02-346.14], p = 0.002). This association was still significant after adjustment to the SOFA (Sequential Organ Failure Assessment) score. A model including a high SOFA score and a core-to index finger >7 °C was effective to predict day-8 mortality (c-statistic: 0.8735 [0.770-0.976]). Core-to-index finger temperature gradient was correlated with CRT, Mottling Score, and arterial lactate levels. CONCLUSIONS: Core-to-index finger temperature gradient higher than 7 °C predicts day-8 mortality in septic shock and is correlated with other tissue perfusion markers.

Use of infrared thermography to detect early alterations of peripheral perfusion: evaluation in a porcine model.

This study aimed to evaluate the variations of infrared thermography according to rapid hemodynamic changes, by measuring the peripheral skin temperature in a porcine model. Eight healthy piglets were anesthetized and exposed to different levels of arterial pressure. Thermography was performed on the left forelimb to measure carpus and elbow skin temperature and their associated gradient with the core temperature. Changes in skin temperature in response to variations of blood pressure were observed. A negative correlation between arterial pressure and temperature gradients between peripheral and core temperature and a negative correlation between cardiac index and these temperature gradients were observed. Thermography may serve as a tool to detect early changes in peripheral perfusion.

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.