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.

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 the nociception-antinociception balance using the Parasympathetic Tone Activity index in dogs anaesthetized for castration.

OBJECTIVE: To evaluate the performance of the Parasympathetic Tone Activity (PTA) index in assessing the nociception-antinociception balance in anaesthetized dogs undergoing castration. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of 22 healthy client-owned dogs. METHODS: The dogs underwent general anaesthesia, with continuous monitoring of mean and instantaneous PTA (PTAm, PTAi), mean arterial pressure and heart rate. The values of these variables were divided according to the occurrence or absence of a haemodynamic reaction (HDR) at different time points: during surgical preparation, cutaneous incision, testicles extraction, cutaneous suture, after fentanyl administration, and after dexmedetomidine administration during recovery. Data were collected initially and 1, 3 and 5 minutes after each time point. The performance of the dynamic variation of the PTA (ΔPTA) to predict HDR or its resolution within 3 or 5 minutes was assessed using receiver operating characteristic (ROC) curves analysis. A p value < 0.05 was considered significant. RESULTS: During HDR, a decrease in PTAi (-34% and -31%) and PTAm (-26% and -30%) occurred at 3 (p = 0.005; p = 0.004) and 5 minutes (p = 0.001), respectively. After fentanyl administration, a decrease in haemodynamic variables occurred with a 45% increase in PTAi (p = 0.004). The ROC curve analysis of pooled data of the ΔPTAi for the prediction of HDR within 3 minutes indicated an area under the curve (AUC) of 0.70 (p = 0.0016) (threshold value: -16%). After fentanyl administration, the ROC curve analysis of ΔPTAi for the prediction of resolution of HDR within 3 minutes indicated an AUC of 0.69 (threshold value: +12%). CONCLUSIONS AND CLINICAL RELEVANCE: The PTAi appears to be an interesting tool to assess the nociception-antinociception balance. However, further studies with a variety of clinical scenarios and anaesthesia protocols are required to conclude on its performance.

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.

Effects of methylene blue on microcirculatory alterations following cardiac surgery: A prospective cohort study.

BACKGROUND: Methylene blue is used as rescue therapy to treat catecholamine-refractory vasoplegic syndrome after cardiac surgery. However, its microcirculatory effects remain poorly documented. OBJECTIVE: We aimed to study microcirculatory abnormalities in refractory vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass and assess the effects of methylene blue. DESIGN: A prospective open-label cohort study. SETTING: 20-Bed ICU of a tertiary care hospital. PATIENTS: 25 Adult patients receiving 1.5 mg kg-1 of methylene blue intravenously for refractory vasoplegic syndrome (defined as norepinephrine requirement more than 0.5 µg kg-1 min-1) to maintain mean arterial pressure (MAP) more than 65 mmHg and cardiac index (CI) more than 2.0 l min-1 m-2. MAIN OUTCOME MEASURES: Complete haemodynamic set of measurements at baseline and 1 h after the administration of methylene blue. Sublingual microcirculation was investigated by sidestream dark field imaging to obtain microvascular flow index (MFI), total vessel density, perfused vessel density and heterogeneity index. Microvascular reactivity was assessed by peripheral near-infrared (IR) spectroscopy combined with a vascular occlusion test. We also performed a standardised measurement of capillary refill time. RESULTS: Despite normalised CI (2.6 [2.0 to 3.8] l min-1 m-2) and MAP (66 [55 to 76] mmHg), patients with refractory vasoplegic syndrome showed severe microcirculatory alterations (MFI < 2.6). After methylene blue infusion, MFI significantly increased from 2.0 [0.1 to 2.5] to 2.2 [0.2 to 2.8] (P = 0.008), as did total vessel density from 13.5 [8.3 to 18.5] to 14.9 [10.1 to 14.7] mm mm-2 (P = 0.02) and perfused vessel density density from 7.4 [0.1 to 11.5] to 9.1 [0 to 20.1] mm mm-2 (P = 0.02), but with wide individual variation. Microvascular reactivity assessed by tissue oxygen resaturation speed also increased from 0.5 [0.1 to 1.8] to 0.7 [0.1 to 2.7]% s-1 (P = 0.002). Capillary refill time remained unchanged throughout the study. CONCLUSION: In refractory vasoplegic syndrome following cardiac surgery, we found microcirculatory alterations despite normalised CI and MAP. The administration of methylene blue could improve microvascular perfusion and reactivity, and partially restore the loss of haemodynamic coherence. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04250389.

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.

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.

Performance of the Parasympathetic Tone Activity (PTA) index to assess the intraoperative nociception using different premedication drugs in anaesthetised dogs.

The dynamic variations of the Parasympathetic Tone Activity (PTA) index were evaluated to assess nociception in dogs undergoing anaesthetic protocols with different premedication drugs. Sixty-six dogs, divided into three groups of 22 dogs each, were given different premedication drugs "morphine" (0.2 mg/kg), "morphine + medetomidine (5 µg/kg)", "morphine + acepromazine (0.03 mg/kg)", then similarly induced and maintained under general anaesthesia. The PTA, HR (heart rate) and MAP (mean arterial pressure) were assessed at S (steady-state), Cut (cutaneous incision), PTAE (PTA Event, assessed 1 min before a significant PTA decrease), HDR (Haemodynamic reaction, assessed 5 min before an increase of ≥ 20% in HR and/or MAP). For each group, the dynamic variation of PTA (ΔPTA) was calculated and a Receiver Operating Characteristics (ROC) curve was performed to detect if any of the premedication drugs may alter the performance of PTA index to predict intraoperative haemodynamic reactions. In all groups, a haemodynamic reaction was detected after Cut, PTAE and HDR and was preceded with a significant decrease of PTA, except for "morphine + medetomidine" group which showed a significant drop of PTA only at PTAE and HDR. The ΔPTA showed a fair performance in all groups (a mean [95% CI] AUC of 0.73 [0.62-0.82], 0.70 [0.59-0.79] and 0.71 [0.59-0.80] respectively in morphine, morphine + ACP and morphine + medetomidine). Although ΔPTA was rather altered by the premedication drug, it was able to predict, to a certain extent, haemodynamic reactions in all groups.

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 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.

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.

Successful Cardiopulmonary Resuscitation in a Sevoflurane Anaesthetized Horse That Suffered Cardiac Arrest at Recovery.

A 17-year-old mare undergoing dental surgery suffered a cardiac arrest while being transferred from the surgical theatre to the recovery box. This complication was diagnosed early, thus allowing a prompt start to the cardiopulmonary resuscitation maneuvers. External thoracic compressions, intermittent positive pressure ventilation, and adrenaline administration were at the core of this successful resuscitation. Although it was not possible to confirm the cause of cardiac arrest in this horse, a Bezold-Jarisch reflex due to potential decrease on venous return because of postural change and drug interactions was hypothesized. Based on this report, it appears advisable to smoothly change the position of anaesthetized patient; furthermore, the administration of drugs affecting cardiovascular hemodynamics or sympatho-vagal balance to animals while changing their recumbency should be avoided.

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.

Gut and sublingual microvascular effect of esmolol during septic shock in a porcine model.

INTRODUCTION: Esmolol may efficiently reduce heart rate (HR) and decrease mortality during septic shock. An improvement of microcirculation dissociated from its macrocirculatory effect may a role. The present study investigated the effect of esmolol on gut and sublingual microcirculation in a resuscitated piglet model of septic shock. METHODS: Fourteen piglets, anesthetized and mechanically ventilated, received a suspension of live Pseudomonas aeruginosa. They were randomly assigned to two groups: the esmolol (E) group received an infusion of esmolol, started at 7.5 µg⋅kg(-1)⋅min(-1), and progressively increased to achieve a HR below 90 beats⋅min(-1). The control (C) group received an infusion of Ringer's lactate solution. HR, mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), systemic vascular resistance (SVR), arterio-venous blood gas and lactate were recorded. Oxygen consumption (VO2), delivery (DO2) and peripheral extraction (O2ER) were computed. Following an ileostomy, a laser Doppler probe was applied on ileal mucosa to monitor gut microcirculatory laser Doppler flow (GMLDF). Videomicroscopy was also used on ileal mucosa and sublingual areas to evaluate mean flow index (MFI), heterogeneity, ratio of perfused villi and proportion of perfused vessels. Resuscitation maneuvers were performed following a defined algorithm. RESULTS: Bacterial infusion induced a significant alteration of the gut microcirculation with an increase in HR. Esmolol produced a significant time/group effect with a decrease in HR (P <0.004) and an increase in SVR (P <0.004). Time/group effect was not significant for CI and MAP, but there was a clear trend toward a decrease in CI and MAP in the E group. Time/group effect was not significant for SI, O2ER, DO2, VO2, GMLDF and lactate. A significant time/group effect of ileal microcirculation was found with a lower ileal villi perfusion (P <0.025) in the C group, and a trend toward a better MFI in the E group. No difference between both groups was found regarding microcirculatory parameters in the sublingual area. CONCLUSIONS: Esmolol provided a maintenance of microcirculation during sepsis despite its negative effects on macrocirculation. Some parameters even showed a trend toward an improvement of the microcirculation in the gut area in the esmolol group.