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Background: Several reports have confirmed the efficacy of Intralipid® (containing soya bean oil, egg phospholipids, glycerin and water) in the therapy of systemic local anesthetic intoxication. Pretreatment with Intralipid® shifted the dose-response to bupivacaine-induced asystole in rats. Whether intravenous anesthesia with propofol in the widely used medium chain triglyceride lipid emulsion increases the therapeutic range of systemically administered bupivacaine or not is unknown and was investigated in this study.Methods: A total of 30 piglets aged 2-6 weeks and weighing 4.5-6.5 kg were randomized into 2 groups and anesthetized with sevoflurane (group S) alone or with propofol 10 mg/kg body weight (BW)/h plus sevoflurane (group PS). After 60 min of steady state anesthesia arterial blood was sampled for assessment of blood gases, acid-base state and triglyceride plasma concentrations. Thereafter bupivacaine 0.125% was continuously infused by an infusion syringe pump through a central venous line at a rate of 4 mg/kg BW/min until invasively measured mean arterial pressure (MAP) was reduced by 50% of initial value. The bupivacaine infusion was stopped, blood for assessment of bupivacaine plasma concentration was drawn and the spontaneous hemodynamic course was observed. Resuscitation was not attempted. Results are presented as median and range. The Mann-Whitney U-test was used to assess differences between the two groups for triglyceride as well as for bupivacaine plasma concentrations measured at MAP 50%. A p-value≤0.05 was considered to be significant.Results: Baseline conditions (arterial blood pH, plasma protein and triglyceride plasma concentrations) did not differ significantly between the two groups. After 1 h of anesthesia, triglyceride plasma concentrations were significantly increased in group PS (median 0.69 mmol/l) compared to the corresponding baseline values (median 0.14 mmol/l; p<0.001) and to the 1 h values of group S (median 0.16 mmol/l; p<0.001). The total amount of bupivacaine administered was 9 mg/kg BW in both groups (6-13 mg/kg BW in group S, 5-13 mg/kg BW in group PS). Resulting bupivacaine plasma concentrations were 180 μmol/l (83-686 μmol/l) in group S and 185 μmol/l (130-465 μmol/l) in group PS. However, the total amount of bupivacaine administered and bupivacaine plasma concentrations at MAP 50% did not reveal statistically significant differences between the two groups but a huge variability of both parameters within each group was observed. None of the 30 piglets spontaneously recovered and they died from pulseless electrical activity or from asystolic cardiac arrest. The time from MAP 50% until cardiac arrest demonstrated a large variability but did not reveal significant differences between the two groups. The time to cardiac arrest was similar in both groups.Conclusion: Medium/long chain triglyceride lipid emulsion (50:50) as widely used in propofol solutions did not increase therapeutic safety in cases of intravascular bupivacaine administration in this piglet model. [ABSTRACT FROM AUTHOR]

Objective: To compare the cardiovascular effects of a combination of medetomidine and vatinoxan (MVX) versus medetomidine (MED) alone administered intramuscularly (IM) and to determine whether heart rate (HR) can be used as a surrogate for cardiac output (CO) after the use of medetomidine with or without vatinoxan., Study Design: A randomized, blinded, experimental, crossover study., Animals: A group of eight healthy Beagle dogs aged 4.6 (2.3-9.4) years and weighing 12.9 (9-14.7) kg, median (range)., Methods: Each dog was injected with 1 mg m -2 medetomidine with or without 20 mg m -2 vatinoxan IM with a washout period of 7 days. Cardiovascular data and arterial and mixed venous blood gas samples were collected at baseline, 5, 10, 15, 20, 35, 45, 60, 90 and 120 minutes after treatment administration. CO was measured at all time points via thermodilution. Differences between treatments, period and sequence were evaluated with repeated measures analysis of covariance and the relationship between HR and CO was assessed with a repeated measures analysis of variance; p values < 0.05 were deemed significant., Results: The CO was 47-96% lower after MED than after MVX (p < 0.0001). Increases in systemic, pulmonary arterial and right atrial pressures and oxygen extraction ratio were significantly higher after MED than after MVX (all p < 0.0001). HR was significantly lower after MED and the linear relationship to CO was significant (p < 0.0001)., Conclusions and Clinical Relevance: Overall, MED affected the cardiovascular system more negatively than MVX, and the difference in cardiovascular function between the treatments can be considered clinically relevant. HR was linearly related to CO, and decreases in HR reflected cardiac performance for dogs sedated with medetomidine with or without vatinoxan., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the effects of intramuscularly administered acepromazine or dexmedetomidine on buccal mucosa microcirculation in Beagle dogs., Study Design: Experimental, blinded, crossover study., Animals: A group of seven Beagle dogs aged 7.5 ± 1.4 years (mean ± standard deviation)., Methods: Microcirculation was assessed on buccal mucosa using sidestream dark field videomicroscopy. After baseline measurements, 5 μg kg -1 dexmedetomidine or 30 μg kg -1 acepromazine were administered intramuscularly. After 10, 20 and 30 minutes, measurements were repeated. At 40 minutes after premedication, anaesthesia was induced with propofol intravenously and maintained with isoflurane. Measurements were repeated 50, 60 and 65 minutes after the injection of the investigated drugs. Analysed microcirculatory variables were: Perfused de Backer density, Perfused de Backer density of vessels < 20 μm, Proportion of perfused vessels and Proportion of perfused vessels < 20 μm. Heart rate (HR), systolic, diastolic (DAP) and mean (MAP) arterial pressures were recorded at the same time points. Macro- and microcirculatory variables were analysed using a linear mixed model with baseline as a covariate, treatment, trial period and repetition as fixed effects and time and dog as random effect. Results are presented as effect size and confidence interval; p values < 0.05 were considered significant., Results: After acepromazine, Perfused de Backer density was greater during sedation and anaesthesia [3.71 (1.93-5.48 mm mm -2 , p < 0.0001) and 2.3 (0.86-3.75 mm mm -2 , p < 0.003)], respectively, than after dexmedetomidine. HR was significantly lower, whereas MAP and DAP were significantly higher with dexmedetomidine during sedation and anaesthesia (p < 0.0001 for all) compared with acepromazine., Conclusions and Clinical Relevance: The sedative drugs tested exerted a significant effect on buccal mucosal microcirculation with a higher Perfused de Backer density after the administration of acepromazine compared with dexmedetomidine. This should be considered when microcirculation is evaluated using these drugs., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To measure the effects on microcirculation of medetomidine alone (MED) or combined with vatinoxan (MVX)., Study Design: Randomized, crossover, blinded, experimental study., Animals: A group of eight healthy purpose-bred Beagle dogs., Methods: Each dog was given 1 mg m -2 MED intramuscularly (IM) or combined with 20 mg m -2 vatinoxan IM (MVX) with a washout period of 7 days. A sidestream dark field (SDF) camera was placed on the buccal mucosa to assess the oral mucosal microcirculation for perfused DeBacker density, proportion of perfused vessels (PPV) (both for all vessels and vessels with a diameter < 20 μm), microvascular flow index (MFI) and heterogeneity index (HI). Videos were recorded at baseline (-5) and 10, 20, 30, 40, 60, 90 and 120 minutes after treatment administration. Linear mixed-effects models were used to assess if microvascular variables were significantly associated with treatment, baseline, and sequence. Results are presented as estimated effect (95% confidence interval), and a p value < 0.05 was considered significant., Results: The interquartile range for baseline measurements was 91.49%-98.42% for PPV, 2.75-3 for MFI and 0-0.36 for HI. Significant effects of treatment and baseline were found. The estimated effect of MED against MVX was -1.98% (-3.53% to -0.42%) for PPV, -0.33 (-0.43 to -0.22) for MFI and 0.14 (0.05 to 0.22) for HI. There were no significant changes seen for perfused DeBacker density, perfused DeBacker density < 20 μm and PPV < 20 μm between treatments., Conclusions and Clinical Relevance: These results suggest that MVX had significantly fewer effects on buccal mucosal microcirculation than MED. The SDF camera is a useful research tool to assess the microcirculatory status of heavily sedated dogs., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the influence of general anesthesia on rotational thromboelastometry (ROTEM) and standard coagulation testing in healthy dogs., Study Design: Prospective experimental study., Animals: 10 healthy Beagle dogs., Methods: Dogs were administered methadone (0.2 mg/kg) intramuscularly. Anesthesia was co-induced intravenously 30 min later with midazolam (0.1 mg/kg) and propofol to effect, and maintained with sevoflurane. Crystalloids were administered at 5 ml/kg/h. Blood was sampled by direct venipuncture before induction (T0) and 3.5 h later (T3.5) and ROTEM parameters (ExTEM, InTEM, FibTEM, ApTEM), standard plasmatic coagulation tests (prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration), hematology, ionized calcium, triglycerides, pH, lactate and body temperature were compared over time with Students t - test or Wilcoxon matched pairs signed-rank tests., Results: The following variables dropped significantly between T0 and T3.5: body temperature ( p < 0.0001), hematocrit ( p < 0.0001), platelet count ( p < 0.01), pH ( p < 0.01), triglycerides ( p < 0.01), fibrinogen concentration ( p < 0.01), ExTEM, FibTEM ( p < 0.01) and ApTEM ( p < 0.05) clotting times. Lactate concentration ( p < 0.01), aPTT ( p < 0.05) and FibTEM maximum clot firmness increased ( p < 0.05). No changes were noted in ionized calcium, PT and InTEM values., Conclusion and Clinical Relevance: General anesthesia with concurrent hemodilution and hypothermia induced significant but clinically irrelevant changes in coagulation variables measured at 37 °Celsius. Blood samples from anaesthetized animals can be used for determination of coagulation status in dogs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Objectives The aim of this study was to determine in-house reference intervals (RIs) for venous blood analysis with the RAPIDPoint 500 blood gas analyser using blood gas syringes (BGSs) and to determine whether immediate analysis of venous blood collected into lithium heparin (LH) tubes can replace anaerobic blood sampling into BGSs. Methods Venous blood was collected from 24 healthy cats and directly transferred into a BGS and an LH tube. The BGS was immediately analysed on the RAPIDPoint 500 followed by the LH tube. The BGSs and LH tubes were compared using paired t-test or Wilcoxon matched-pairs signed-rank test, Bland-Altman and Passing-Bablok analysis. To assess clinical relevance, bias or percentage bias between BGSs and LH tubes was compared with the allowable total error (TEa) recommended for the respective parameter. Results Based on the values obtained from the BGSs, RIs were calculated for the evaluated parameters, including blood gases, electrolytes, glucose and lactate. Values derived from LH tubes showed no significant difference for standard bicarbonate, whole blood base excess, haematocrit, total haemoglobin, sodium, potassium, chloride, glucose and lactate, while pH, partial pressure of carbon dioxide and oxygen, actual bicarbonate, extracellular base excess, ionised calcium and anion gap were significantly different to the samples collected in BGSs ( P <0.05). Furthermore, pH, partial pressure of carbon dioxide and oxygen, extracellular base excess, ionised calcium and anion gap exceeded the recommended TEa. Conclusions and relevance Assessment of actual and standard bicarbonate, whole blood base excess, haematocrit, total haemoglobin, sodium, potassium, chloride, glucose and lactate can be made based on blood collected in LH tubes and analysed within 5 mins. For pH, partial pressure of carbon dioxide and oxygen, extracellular base excess, anion gap and ionised calcium the clinically relevant alterations have to be considered if analysed in LH tubes.

The aims of this study were to measure plasma levels of R- and S-ketamine and their major metabolites R- and S-norketamine following single intravenous bolus administration of racemic or S-ketamine in sevoflurane anaesthetised dogs and to calculate the relevant pharmacokinetic profiles. Six adult healthy beagle dogs were used in the study. An intravenous bolus of 4mg/kg racemic ketamine (RS-KET) or 2mg/kg S-ketamine (S-KET) was administered, with a three-weeks washout period between treatments. Venous blood samples were collected at fixed times until 900min and R- and S-ketamine as well as R- and S-norketamine plasma levels determined by liquid chromatography coupled with tandem mass spectrometry. Cardiovascular parameters were recorded during the anaesthesia until 240min. All dogs recovered well from anaesthesia. No statistical differences between groups were detected in any cardiovascular parameter. The pharmacokinetics of S-ketamine did not differ when injected intravenously alone or as part of the racemic mixture in dogs anaesthetised with sevoflurane. Following racemic ketamine, the area under the curve of R-norketamine was statistically higher than the one of S-norketamine., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To establish reference intervals for rotational thromboelastometry (ROTEM) using feline blood., Design: Prospective study., Setting: University teaching hospital., Animals: Twenty-three clinically healthy cats between 1 and 15 years., Intervention: For each cat, whole blood was collected via jugular or medial saphenous venipuncture, and blood was placed into a serum tube, a tube containing potassium-EDTA, and tubes containing 3.2% sodium citrate. The tubes were maintained at 37°C for a maximum of 30 minutes before coagulation testing., Measurements and Main Results: ROTEM tests included the EXTEM, INTEM, FIBTEM, and APTEM assays. In addition, prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen concentration (Clauss method) were analyzed for each cat. Reference intervals for ROTEM were calculated using the 2.5-97.5 th percentile for each parameter, and correlation with the standard coagulation profile was performed. Compared to people, clinically healthy cats had similar values for the EXTEM and INTEM assays, but had lower plasma fibrinogen concentrations (0.9-2.2 g/L), resulting in weaker maximum clot firmness (MCF, 3-10 mm) in the FIBTEM test. In 18 cats, maximum lysis (ML) values in the APTEM test were higher than in the EXTEM test, which seems unlikely to have occurred in the presence of aprotinin. It is possible that the observed high maximum lysis values were due to clot retraction rather than true clot lysis. Further studies will be required to test this hypothesis., Conclusions: Cats have a weaker clot in the FIBTEM test, but have a similar clot strength to human blood in the other ROTEM assays, which may be due to a stronger contribution of platelets compared to that found in people. In cats, careful interpretation of the results to diagnose hyperfibrinolysis is advised, especially with the APTEM test, until further data are available., (© Veterinary Emergency and Critical Care Society 2017.)

This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and received morphine intramuscularly. The sciatic and femoral nerves of the leg to be operated on were located using a nerve stimulator (1 Hz, 0.5 mA). Rabbits were assigned to a treatment group (LB; n = 12) or a placebo group (P; n = 12) in a randomized blinded fashion. Group LB received lidocaine 2% (1 mg/kg) combined with bupivacaine 0.5% (0.25 mg/kg) injections around the sciatic and femoral nerves (0.1 mL/kg total volume per site) and subcutaneous infiltration of the incision site with lidocaine 1% (1.25 mg/kg). Group P received the same volume of 0.9% NaCl. Rabbits in group P required higher doses of intraoperative fentanyl and propofol to reduce heart rate and suppress increase in systolic blood pressure, and maintain an adequate anaesthetic plane. Interventional analgesia (buprenorphine and carprofen) was required significantly earlier in rabbits in group P (2 and 6 h after the first nerve blockade, respectively) based on assessment of their pain-related behaviour and range of motion. Using a visual analogue scale (0 mm= no pain to 100 mm= maximal possible pain), rabbits in group LB were judged to show significantly less pain compared with rabbits in group P (14 ± 10 mm and 37 ± 25 mm, respectively) 2 h after nerve blockade. In conclusion, this technique of perineural analgesia combined with incision site infiltration reduced intraoperative fentanyl requirements and improved postoperative analgesia in rabbits.

Objectives: To evaluate cardiopulmonary effects and anaesthesia recovery quality in horses anaesthetized with isoflurane receiving medetomidine or S-ketamine infusions., Study Design: Randomized, blinded, prospective clinical trial., Animals: Fifty horses undergoing elective surgery., Methods: After acepromazine and flunixin meglumine premedication, horses received medetomidine (7 μg kg -1 ) intravenously (IV). Anaesthesia was induced with midazolam and racemic ketamine (Med treatment group; 2.2 mg kg -1 ; n = 25) or S-ketamine (S-ket treatment group; 1.1 mg kg -1 ; n = 25) IV and maintained with isoflurane in oxygen/air and medetomidine (Med; 3.5 μg kg -1 hour -1 ) or S-ketamine (S-ket; 0.5 mg kg -1 hour -1 ). All horses were mechanically ventilated. Cardiopulmonary variables were evaluated. Isoflurane end-tidal concentrations (Fe'Iso), dobutamine requirements and thiopental boli were recorded. Plasma samples were collected in six horses to evaluate S-ketamine and S-norketamine concentrations. After surgery, medetomidine 2 μg kg -1 was administered IV. Four independent observers scored recovery using a visual analogue scale and a numerical rating scale., Results: Both groups required similar mean Fe'Iso (1%). However, S-ket horses needed more thiopental boli. Median intraoperative cardiac index values were higher with S-ket (4.5 L minute -1  m -2 ) than Med (3.9 L minute -1  m -2 ). Overall, there were no differences in heart rate, blood pressure or dobutamine requirements; however, horses in S-ket showed higher heart rate values at 30 minutes after anaesthesia induction. Compared with Med horses, S-ket horses showed decreased PaO 2 and increased pulmonary venous admixture values estimated with the Fshunt calculation. Recoveries were shorter and of poorer quality with S-ket. During infusion, S-ketamine and S-norketamine plasma concentrations lay in the ranges of 0.209-0.917 μg mL -1 and 0.250-0.723 μg mL -1 , respectively., Conclusions and Clinical Relevance: Despite the higher intraoperative cardiac index with S-ket, both protocols were considered to provide acceptable cardiovascular function. However, recovery quality was significantly better in the Med group., (© 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To assess agreement and trending ability of transpulmonary thermodilution (TPTD), calibrated pulse contour (PiCCO), and pulse power (PulseCO) methods compared to pulmonary artery thermodilution (PATD) for determination of cardiac output (CO) in anesthetized dogs., Design: Experimental, prospective study., Setting: University teaching hospital., Animals: Six adult Beagle dogs., Interventions: Dogs were anesthetized with sevoflurane and instrumented with pulmonary and femoral artery thermodilution catheters. CO was measured at baseline and at 5, 15, 30, 45, 60, 120, 180, and 240 minutes after IV administration of ketamine or s-ketamine. Baseline PATD and TPTD calibrated PulseCO and PiCCO, respectively. Agreement and trending ability was analyzed with Bland-Altman, concordance, and polar plot methodology., Measurements and Main Results: Median (range) CO values of 2.27 (0.98-3.4) L/min were measured with PATD, and 2.8 (1.9-4.04) L/min with TPTD, which resulted in a mean bias (± standard deviation) of -0.66 (± 0.36) L/min. Concordance rate was 91% and radial limits of agreement (RLOA) were ±35°. PATD against PiCCO resulted in a mean bias of -0.71 (± 0.62) L/min and PATD against PulseCO in a mean bias of 0.13 (± 0.46) L/min. The continuous techniques resulted in concordance rates of 77% for PATD-PiCCO and 74% for PATD-PulseCO and RLOA of ±57° and ±60°, respectively., Conclusions: Intermittent TPTD showed marginal trending ability, while continuous pulse contour and pulse power methods showed poor trending ability over a 4-hour period. The poor performance and possible side effects of the methods tested in this study suggest that they should not be recommended for use in critical patients., (© Veterinary Emergency and Critical Care Society 2016.)

Objective: To evaluate the non-calibrated, minimally invasive cardiac output (CO) monitor FloTrac/Vigileo (FloTrac) against thermodilution (TD) CO in standing horses., Study Design: Prospective, experimental trial., Animals: Nine adult horses weighing a median (range) of 535 (470-602) kg., Methods: Catheters were placed in the right atrium, pulmonary artery and carotid artery under local anaesthesia. CO was measured 147 times by TD and FloTrac and indexed to body weight. Changes in CO were achieved with romifidine or xylazine and dobutamine constant rate infusions. Bland-Altman analysis, concordance and polar plot analysis were used to assess agreement and ability to track changes in CO., Results: Mean ± standard deviation COTD of 48 ± 16 mL kg(-1) minute(-1) (range: 19-93 mL kg(-1) minute(-1) ) and mean COF loTrac of 9 ± 3 mL kg(-1) minute(-1) (range: 5-21 mL kg(-1) minute(-1) ) were measured. Low agreement with a large mean bias of 39 mL kg(-1) minute(-1) and wide limits of agreement of 8-70 mL kg(-1) minute(-1) were found. The percentage error of 108% and precision of TD of ± 18% resulted in an estimated precision of FloTrac of ± 106%. Comparison of changes in COF loTrac with changes in COTD gave a concordance rate of 52% in the four-quadrant plot, and a mean polar angle of -11° with radial limits of agreement of ± 61 ° in the polar plot. Mean arterial pressure (MAP) and COF loTrac were positively correlated (r = 0.5, p < 0.0001). No correlation of MAP with COTD was observed., Conclusions and Clinical Relevance: The FloTrac system, originally designed for use in humans, neither measured absolute CO in standing horses accurately nor tracked relative changes in CO measured by TD correctly. The false dependence of COF loTrac on arterial blood pressure further discourages the use of this technique in horses., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To compare the agreement, repeatability and trending ability of transpulmonary thermodilution (TPTD) and pulmonary artery thermodilution (PATD) cardiac output (Q˙t) measurements in unsedated newborn calves., Study Design: Prospective experimental trial., Animals: Eight newborn calves weighing a median (range) of 53 (46-59) kg., Methods: Pulmonary and femoral artery thermodilution catheters were placed under local anaesthesia. A total of 382 PATD and TPTD Q˙t measurements were performed simultaneously. Cardiac output was influenced by intravenous doxapram and theophylline in a randomized crossover fashion. Bland-Altman analysis for multiple comparisons, concordance and polar plots were used to assess TPTD against PATD., Results: Median (range) cardiac index values measured with PATD and TPTD were 197 mL kg(-1) minute(-1) (74-335 mL kg(-1) minute(-1)) and 196 mL kg(-1) minute(-1) (59-395 mL kg(-1) minute(-1)), respec-tively. A small mean bias of -3 mL kg(-1) minute(-1) with limits of agreement (LOA) of -64 to 58 mL kg(-1) minute(-1) and a percentage error of 31% were found. Eighty-two mean values were calculated. This reduced the LOA to -50 to 41 mL kg(-1) minute(-1) with a similar small bias and a percentage error of 23%. Mean TPTD tracked changes in Q˙t compared with mean PATD with 90% concordance, a mean polar angle of 6° and radial LOA of 43°, indicating marginal trending ability. Keeping the femoral artery catheter patent and obtaining acceptable measurements were very challenging because the calves were not used to being restrained. Calf movement had less influence on PATD., Conclusions and Clinical Relevance: We recommend that PATD remains the reference method to measure Q˙t in unsedated newborn calves. However, the robust results of the evaluation of the less invasive TPTD technique warrants further evaluation taking into account the difficulties reported in this study., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

The present study evaluated transpulmonary thermodilution (TPTD) and pulse contour cardiac output (PCCO) both measured by the PiCCO Plus™ monitor (Pulsion Medical Systems, Munich, Germany) against pulmonary artery thermodilution (PATD) in cats as a hemodynamic model for small children. A wide range of cardiac outputs (CO) was simultaneously measured. Accuracy and trending abilities were critically evaluated. Three cats were studied under isoflurane anesthesia and 160 CO measurements were performed with 3 mL ice-cold 5 % dextrose with PATD and TPTD. The results were compared with the PCCO measurement before the bolus measurement. Cardiac output was manipulated from 32 to 224 mL/kg/min by dobutamine, dopamine, phenylephrine, medetomidine and increased concentrations of isoflurane. Bland-Altman analysis, concordance and polar plot analysis were performed to assess accuracy and trending ability. TPTD was measuring constantly higher than PATD with a mean bias of 73 mL/kg/min and limits of agreement of 34-112 mL/kg/min, a concordance rate of 94 % and a mean polar angle of -5° with radial limits of agreement (RLOA) of 33°. Concordance rate of the PCCO versus PATD was 82 % with a mean polar angle of -10° and RLOA of 46° and versus TPTD 90 % with a mean polar angle of -6° and RLOA of 46°. Both tested methods constantly overestimated simultaneous PATD measurements. The small size, low flows and the relative short catheter not reaching the abdominal aorta may explain that. However TPTD tracked changes accurately opposed to a poor trending ability of the PCCO measurement.

The aim of this study was to test the effect of cardiac output (CO) and pulmonary artery hypertension (PHT) on volumetric capnography (VCap) derived-variables. Nine pigs were mechanically ventilated using fixed ventilatory settings. Two steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO was increased by 50% from baseline (COup) with an infusion of dobutamine≥5 μg kg(-1) min(-1) and decreased by 40% from baseline (COdown) infusing sodium nitroglycerine≥30 μg kg(-1) min(-1) plus esmolol 500 μg kg(-1) min(-1). Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07). Invasive hemodynamic data and VCap were recorded and compared before and after each step using a mixed random effects model. Compared to baseline, the normalized slope of phase III (SnIII) increased by 32% in PHT25 and by 22% in PHT40. SnIII decreased non-significantly by 4% with COdown. A combination of PHT and COdown associated with severe hypoxemia increased SnIII by 28% compared to baseline. The elimination of CO2 per breath decreased by 7% in PHT40 and by 12% in COdown but increased only slightly with COup. Dead space variables did not change significantly along the protocol. At constant ventilation and body metabolism, pulmonary artery hypertension and decreases in CO had the biggest effects on the SnIII of the volumetric capnogram and on the elimination of CO2.

Background and Objectives: Impairment of blood coagulation is one of the main side effects of volume replacement, particularly if artificial colloids such as hydroxyethyl starch (HES) and gelatine preparations are used. This animal study aimed to evaluate the effect of a single fast intravenous crystalloid or colloid fluid bolus on blood coagulation as measured by rotation thromboelastometry (ROTEM)., Methods: Thirty-two anesthetized piglets were infused with a rapid 20 ml·kg(-1) fluid bolus of either normal saline (NS), 4% gelatine, 5% albumin or 6% HES 130/0.4 (n = 8 per group) over a period of 2 min. Hemostasis was assessed by ROTEM before and 1 min after fluid administration. Within-group differences were analyzed by Wilcoxon test, and additionally overall Kruskal-Wallis test followed by posthoc Mann-Whitney U-test were applied to detect differences between groups., Results: All fluids caused a significant weakening of clot strength within groups. HES and gelatine showed a significantly stronger impairment of clot growth and maximum clot firmness as compared with albumin and normal saline. Impairment of fibrin polymerization was more pronounced following HES as compared with all other fluids., Conclusion: After moderate but very fast volume loading, HES and gelatine impair blood coagulation to a larger extent as compared with albumin or normal saline, while no significant differences were observed between both artificial colloids., (© 2012 Blackwell Publishing Ltd.)

Background: Modern high volume-low pressure (HVLP) endotracheal tubes (ETT) cuffs can seal the trachea using baseline cuff pressures (CP) lower than peak inspiratory airway pressures (PIP). The aim of the study was to determine whether this technique reduces the damage to the tracheal mucosa compared to constant CP of 20 cmH(2)O., Methods: Eighteen piglets were intubated with an ID 4.0 mm HVLP cuffed ETT (Microcuff PET) and artificially ventilated with 20 cmH(2)O PIP and 5 cmH(2)O PEEP. Animals were randomly allocated to two groups of CP: group A (just seal; n = 9) and group B (20 cmH(2)O; n = 9), controlled constantly with a manometer during the following 4-h study period under sevoflurane anesthesia. After euthanasia, cuff position was marked in situ. Damage in the cuff region was evaluated with scanning electron microscopy (SEM) examination by grading of mucosal damage and by estimating percentage of intact mucosal area both by a blinded observer., Results: Maximal CP to seal the trachea in group A ranged from 12 to 18 cmH(2)O (median: 14 cmH(2)O). Using a mixed effects model approach, the estimated mean effect of group B vs group A was an increase of 17.9% (SE 8.1%) higher proportion of pictures with an area of at least 5% intact mucosa (P = 0.042)., Conclusion: Minimal sealing pressures with cyclic pressure changes from CP did not result in decreased damage to the tracheal mucosa compared to constant CP of 20 cmH(2)O in this short-term animal trial., (© 2012 Blackwell Publishing Ltd.)

Objective: To evaluate the accuracy of a new cardiac output monitor (FloTrac/Vigileo), originally designed for humans, in dogs. This pulse contour cardiac output monitoring system cannot be calibrated and measures cardiac output (Q̇t) from a standard arterial catheter., Study Design: Prospective experimental trial., Animals: Eight adult Beagle dogs weighing 13.1 (9.8-17.1) kg [median (range)]., Methods: Anaesthesia in the dogs was maintained using isoflurane. A pulmonary artery catheter and a metatarsal arterial catheter (22 gauge) were placed. Cardiac output was measured simultaneously 331 times by thermodilution and FloTrac technique. A broad spectrum of Q̇t measurements was achieved through alterations of isoflurane concentration, administration of propofol boluses and dobutamine infusions. Agreement between the methods was quantified with Bland Altman analysis and disagreement was assessed with linear mixed models. Results  Median (10th and 90th percentile) cardiac output as measured with thermodilution was 2.54 (1.47 and 5.15) L minute(-1) and as measured with FloTrac 8.6 (3.9 and 17.3) L minute(-1) . FloTrac measurements were consistently higher with a mean bias of 7 L minute(-1) and limits of agreement of -3.15 to 17.17 L minute(-1) . Difference between the methods was most pronounced in high Q̇t measurements. Linear mixed models showed an estimated difference between the two methods of 8.05 (standard error 1.18) L minute(-1) and a significant interaction between mean arterial pressure and method. Standard deviation (4.45 higher) with the FloTrac method compared to thermodilution was increased., Conclusion: Compared to thermodilution measurements, the FloTrac system was influenced to a higher degree by arterial blood pressure, resulting in consistent overestimation of cardiac output., Clinical Relevance: The FloTrac monitor, whose algorithms were developed based on human data, cannot be used as an alternative for thermodilution in dogs., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

In veterinary medicine, point-of-care testing (POCT) techniques have become popular, since they provide immediate results and only small amounts of blood are needed. However, their accuracy is controversial. Pigs are often used for research purposes and accurate measurement of haemoglobin (Hb) is important during invasive procedures. The aim of this study was to evaluate two different Hb POCT devices in neonatal pigs. A prospective study with 57 pigs of 3-6 weeks of age, weighing 4.1-6.2 kg (median 5.1 kg) was performed. Fifty-seven blood samples were analysed for Hb using a conductivity-based and a photometrical POCT device and compared with a photometrical reference method. Statistical analysis was performed with Bland-Altman analysis, Spearman correlation and Passing-Bablok regression analysis. Hb values ranged from 32 to 108 g/L (median 80 g/L) using the reference method. The bias of the photometrical method (HemoCue(®)) to the reference method was -1 g/L, with limits of agreement (LOA) of -7 to 6 g/L. The conductivity-based method (i-STAT(®)) had a bias of -15 g/L with LOA from -24 to -6 g/L. There was a significant association between protein values and the bias of i-STAT versus CellDyn (r(2) = 0.27, P < 0.05) but not with the bias of HemoCue versus CellDyn (r(2) = 0.001, P = 0.79). The lower the protein values were, the lower the Hb values were measured by the i-STAT. The conductivity-based measurement of Hb constantly underestimated Hb values, whereas the photometrical method demonstrated a better accuracy and is therefore more reliable for on-site measurement of Hb in pigs.

This study aimed to assess intrarater and interrater variability of coagulation point-of-care testing (POCT) using ROTEM delta operated by trained staff. Arterial blood samples were taken from 43 anesthetized piglets aged up to 6 weeks and weighing 4-6 kg. The following clotting measurements were recorded: clotting time, clot formation time (CFT), maximum clot firmness (MCF) and alpha angle using ROTEM delta assays ExTEM, InTEM, FibTEM and ApTEM. Intrarater variability was assessed when a single operator performed the same assay simultaneously in all four channels of the ROTEM device. Interrater variability was assessed by two different operators simultaneously performing the same assay. Variance components of the data were analyzed using linear mixed modeling. Three hundred and forty-three tests from 86 samples were loaded and analyzed. The intraclass correlation coefficient (ICC) was more than 0.7 for clotting measurements except for CFT and alpha in InTEM. For intrarater and interrater assessment, different relative variability for the ROTEM measurements were found with consistently higher variability for clotting time and CFT and lower variability of MCF and alpha angle. Interrater variability was not statistically significant as supported using Akaike's information criterion. Piglet coagulation testing using ROTEM delta showed a high ICC. Variability was significantly lower in MCF and angle alpha compared with clotting time and CFT. No further variability was added by a second user. Based on these data, ROTEM delta appears to be suitable as POCT.

Purpose: Systemic local anesthetic (LA) toxicity resulting from inadvertent intravascular injection of LA is a rare but potentially fatal event. Early recognition of intravascular injection and approaches to improve therapeutic safety are required. This study investigated the influence of intravascular injection dose rate of bupivacaine on bupivacaine plasma levels and timing of LA-induced cardiovascular compromise., Methods: Forty-five piglets, anesthetized with sevoflurane, were randomized into three groups. Bupivacaine was intravenously infused at a rate of 1, 4, or 16 mg/kg/min (groups A, B, and C, respectively) until mean arterial pressure (MAP) dropped to 50% of initial value. Thereafter, bupivacaine infusion was stopped and spontaneous hemodynamic course was observed. Time to MAP 50%, amount of bupivacaine infused, bupivacaine plasma level at infusion stop, spontaneous survivors, or time from bupivacaine stop to circulatory arrest were recorded., Results: Median time to MAP 50% was 297, 119, and 65 s, respectively, in groups A, B, and C (P < 0.001). Median corresponding total amounts of bupivacaine infused were 5.0, 7.8, and 17.0 mg/kg (P < 0.01), and median bupivacaine plasma levels were 53.8, 180.0, and 439.8 μmol/l (P < 0.001). Five of 15 piglets in group A recovered spontaneously; in groups B and C, all animals died within 120 and 21 s, respectively., Conclusion: Higher dose rates of bupivacaine showed much higher plasma bupivacaine levels related to absolute infused dose at MAP 50% and were associated with an increased mortality. Slow administration of LA is recommended to allow timely detection and stopping of inadvertent intravascular administration.

Background: Intravascular application of a small dose of local anesthetics (LA) with epinephrine as well as larger doses of LA under sevoflurane anesthesia results in increase in T-wave amplitude in the electrocardiogram (ECG). The aim of this study was to elucidate whether propofol anesthesia affects these ECG alterations or not., Methods: Thirty neonatal pigs were randomized into two groups. Group 1 was anesthetized with sevoflurane, group 2 with sevoflurane plus continuous propofol infusion (10 mg·kg(-1)·h(-1)). A test dose of 0.2 ml·kg(-1) bupivacaine 0.125% + epinephrine 1 : 200,000 was injected intravenously. Arterial pressure was monitored. ECG was analyzed for changes in T-wave amplitude (positive if ≥25% baseline) and heart rate. In another setting, bupivacaine 0.125% was intravenous infused at a rate of 4 mg·kg(-1)·min(-1). ECG was analyzed for alteration in T-wave amplitude and heart rate at 1.25, 2.5, and 5 mg·kg(-1) bupivacaine infused., Results: T-wave elevation after the administration of an epinephrine containing LA test dose was similar between the two groups. Increase in heart rate caused by the test dose were significantly higher in group 2 (P = 0.008). During continuous bupivacaine administration, T-wave elevation occurred in 40% and 71% (group 1 and 2) at 1.25 mg·kg(-1), in 80% and 100% at 2.5 mg·kg(-1), and in 93% and 86% at 5 mg·kg(-1) bupivacaine infused., Conclusion: Continuous propofol infusion does not suppress the ECG signs of a systemically administered epinephrine containing LA test dose nor does it suppress the ECG signs caused by high doses of intravenous applied bupivacaine., (© 2010 Blackwell Publishing Ltd.)

Background: It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine., Methods: Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg(-1) bupivacaine infused., Results: Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93% and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg(-1) infused., Conclusions: Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administered.

Respiratory stimulants are widely used in asphyxic neonatal calves despite a lack of data about their effectiveness and indications of possible side effects. The effect of doxapram and theophylline on respiratory, cardiovascular, and acid-base variables was investigated in 10 healthy neonatal calves (Bos Taurus). A venous, a peripheral arterial, and a pulmonary arterial catheter were placed, and central venous, pulmonary, and systemic blood pressures and cardiac output were measured using thermodilution technique. Doxapram, but not theophylline, led to an immediate increase in respiratory rate (P

Background: Origin of electrocardiographic (ECG) alterations during intravascular injection of local anaesthetic solutions is controversial. The aim of this study was to elucidate whether epinephrine, bupivacaine or their combination is responsible for ECG alteration., Methods: Forty-five piglets were randomized into three groups. After induction of general anaesthesia using sevoflurane and peripheral venous cannulation, the trachea was intubated, the lungs were artificially ventilated, and anaesthesia was maintained by sevoflurane. Under steady state 0.2 ml kg(-1) and after 10 min 0.4 ml kg(-1) of one of the following three test solutions was administered i.v.: bupivacaine 0.125% (Group 1), bupivacaine 0.125%+epinephrine 1:200 000 (Group 2), and plain epinephrine 1:200,000 (Group 3). The ECG was analysed for alterations in heart rate and T-elevation., Results: After injection of 0.2 or 0.4 ml kg(-1) test solution, an increase in heart rate of at least 10% was found in none of Group 1 and in all of Groups 2 and 3. After application of 0.2 ml kg(-1) test solution, T-elevation was found in 7% of Group 1 and in 93% of Groups 2 and 3. The injection of 0.4 ml kg(-1) revealed a T-elevation in 27%, 100%, and 100%, respectively, in Groups 1, 2, and 3., Conclusions: This animal model demonstrated that increases in heart rate and T-elevation in the ECG during i.v. application of a common test dose (0.2 ml kg(-1)) of bupivacaine are caused by epinephrine addition. Whether higher doses of bupivacaine alone can cause similar ECG changes or not requires further studies.

Objective: To compare anesthesia recovery quality after racemic (R-/S-) or S-ketamine infusions during isoflurane anesthesia in horses., Animals: 10 horses undergoing arthroscopy., Procedures: After administration of xylazine for sedation, horses (n = 5/group) received R-/S-ketamine (2.2 mg/kg) or S-ketamine (1.1 mg/kg), IV, for anesthesia induction. Anesthesia was maintained with isoflurane in oxygen and R-/S-ketamine (1 mg/kg/h) or S-ketamine (0.5 mg/kg/h). Heart rate, invasive mean arterial pressure, and end-tidal isoflurane concentration were recorded before and during surgical stimulation. Arterial blood gases were evaluated every 30 minutes. Arterial ketamine and norketamine enantiomer plasma concentrations were quantified at 60 and 120 minutes. After surgery, horses were kept in a padded recovery box, sedated with xylazine, and video-recorded for evaluation of recovery quality by use of a visual analogue scale (VAS) and a numeric rating scale., Results: Horses in the S-ketamine group had better numeric rating scale and VAS values than those in the R-/S-ketamine group. In the R-/S-ketamine group, duration of infusion was positively correlated with VAS value. Both groups had significant increases in heart rate and mean arterial pressure during surgical stimulation; values in the R-/S-ketamine group were significantly higher than those of the S-ketamine group. Horses in the R-/S-ketamine group required slightly higher end-tidal isoflurane concentration to maintain a surgical plane of anesthesia. Moderate respiratory acidosis and reduced oxygenation were evident. The R-norketamine concentrations were significantly lower than S-norketamine concentrations in the R-/S-ketamine group., Conclusions and Clinical Relevance: Compared with R-/S-ketamine, anesthesia recovery was better with S-ketamine infusions in horses.

Impaired insulin sensitivity is increasingly recognised in cats, but sequences of genes involved in insulin-signalling are largely undetermined in this species. In this study, extended feline mRNA sequences were determined for the adiponectin, glucose transporter-1 (GLUT1), GLUT4, peroxisome proliferative activated receptor-gamma1 (PPARgamma1), PPARgamma2, plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MCP-1) and insulin receptor genes. Conserved dog-specific primers identified from human-dog mRNA alignments were used to amplify feline cDNA in the polymerase chain reaction (PCR). The feline sequences determined by this method were used to design feline-specific primers suitable for real-time PCR for quantification of gene expression in insulin sensitive tissues of healthy cats. Partial sequences of feline mRNAs had 86-95% identity with dog and human genes. Expression of adiponectin, GLUT1, GLUT4, PPARgamma1, PPARgamma2, PAI-1 and insulin receptor mRNA was detected and quantified in subcutaneous and visceral fat and skeletal muscle, whereas MCP-1 mRNA was detected in adipose tissue but not in skeletal muscle. Further characterisation of genes related to glucose metabolism in cats will provide additional insights into insulin-signalling mechanisms in this species.

Objective: To determine the effect of inhalation of isoflurane at end-tidal concentrations greater than, equal to, and less than the minimum anesthetic concentration (MAC) on bispectral index (BIS) in chickens. Animals-10 chickens., Procedures: For each chicken, the individual MAC of isoflurane was determined by use of the toe-pinch method. After a 1-week interval, chickens were anesthetized with isoflurane at concentrations 1.75, 1.50, 1.25, 1.00, and 0.75 times their individual MAC (administered from higher to lower concentrations). At each MAC multiple, a toe pinch was performed and BIS was assessed and correlated with heart rate, blood pressure, and an awareness score (derived by use of a visual analogue scale)., Results: Among the chickens, mean +/- SD MAC of isoflurane was 1.15 +/- 0.20%. Burst suppression was detected at every MAC multiple. The BIS and awareness score were correlated directly with each other and changed inversely with increasing isoflurane concentration. Median (range) BIS values during anesthesia at 1.75, 1.50, 1.25, 1.00, and 0.75 MAC of isoflurane were 25 (15 to 35), 35 (25 to 45), 35 (20 to 50), 40 (25 to 55), and 50 (35 to 65), respectively. Median BIS value at extubation was 70 +/- 9. Values of BIS correlated with blood pressure, but not with heart rate. Blood pressure changed with end-tidal isoflurane concentrations, whereas heart rate did not., Conclusions and Clinical Relevance: Assessment of BIS can be used to monitor the electrical activity of the brain and the degree of unconsciousness in chickens during isoflurane anesthesia.

In sheep, alpha(2)-agonists can induce severe hypoxaemia. In goats, reports on changes in oxygenation are inconsistent. The aim of this study was to compare the cardiopulmonary effects of dexmedetomidine in six goats and four sheep anaesthetised with sevoflurane and maintained at approximately 1 minimal alveolar concentration. The animals were ventilated mechanically and held in an upright position to minimise the influence of positioning on pulmonary function. After baseline cardiopulmonary measures, 2 microg/kg dexmedetomidine was injected intravenously over one minute, and measurements were made for 120 minutes. In both species, respiratory resistance, alveolar dead space and shunt fraction increased and thoracic compliance decreased significantly; arterial, pulmonary arterial, pulmonary capillary wedge and central venous pressures increased and heart rate and cardiac output decreased significantly. Arterial oxygen tension decreased significantly, with no significant difference between the goats and sheep. Wide interindividual differences were observed in both the goats (mean [sd] 144 [149.1] mmHg, range 54.8 to 443.7 mmHg) and sheep (mean [sd] 129.8 [132.1] mmHg, range 33.7 to 352.8 mmHg), but the cardiovascular and respiratory changes were similar in the two species.

Objective: To compare the sedative, anaesthetic-sparing and arterial blood-gas effects of two medetomidine (MED) doses used as pre-anaesthetic medication in sheep undergoing experimental orthopaedic surgery., Study Design: Randomized, prospective, controlled experimental trial., Animals: Twenty-four adult, non-pregnant, female sheep of various breeds, weighing 53.9 +/- 7.3 kg (mean +/- SD)., Methods: All animals underwent experimental tibial osteotomy. Group 0 (n = 8) received 0.9% NaCl, group L (low dose) (n = 8) received 5 microg kg(-1) MED and group H (high dose) (n = 8) received 10 microg kg(-1) MED by intramuscular (IM) injection 30 minutes before induction of anaesthesia with intravenous (IV) propofol 1% and maintenance with isoflurane delivered in oxygen. The propofol doses required for induction and endtidal isoflurane concentrations (F(E')ISO) required to maintain anaesthesia were recorded. Heart and respiratory rates and rectal temperature were determined before and 30 minutes after administration of the test substance. The degree of sedation before induction of anaesthesia was assessed using a numerical rating scale. Arterial blood pressure, heart rate, respiratory rate, FE'ISO, end-tidal CO2 (FE'CO2) and inspired O2 (FIO2) concentration were recorded every 10 minutes during anaesthesia. Arterial blood gas values were determined 10 minutes after induction of anaesthesia and every 30 minutes thereafter. Changes over time and differences between groups were examined by analysis of variance (anova) for repeated measures followed by Bonferroni-adjusted t-tests for effects over time., Results: Both MED doses produced mild sedation. The dose of propofol for induction of anaesthesia decreased in a dose-dependent manner: mean (+/-SE) values for group 0 were 4.7 (+/-0.4) mg kg(-1), for group L, 3.2 (+/-0.4) mg kg(-1) and for group H, 2.3 (+/-0.3) mg kg(-1)). The mean (+/-SE) FE'ISO required to maintain anaesthesia was 30% lower in both MED groups [group L: 0.96 (+/-0.07) %; group H: 1.06 (+/-0.09) %] compared with control group values [(1.54 +/- 0.17) %]. Heart rates were constantly higher in the control group with a tendency towards lower arterial blood pressures when compared with the MED groups. Respiratory rates and PaCO2 were similar in all groups while PaO2 increased during anaesthesia with no significant difference between groups. In group H, one animal developed a transient hypoxaemia: PaO2 was 7.4 kPa (55.7 mmHg) 40 minutes after induction of anaesthesia. Arterial pH values and bicarbonate concentrations were higher in the MED groups at all time points., Conclusion and Clinical Relevance: Intramuscular MED doses of 5 and 10 microg kg(-1) reduced the propofol and isoflurane requirements for induction and maintenance of anaesthesia respectively. Cardiovascular variables and blood gas measurements remained stable over the course of anaesthesia but hypoxaemia developed in one of 16 sheep receiving MED.

Objective: To determine whether inhaled nitric oxide (NO) prevents pulmonary hypertension and improves oxygenation after i.v. administration of a bolus of dexmedetomidine in anesthetized sheep., Animals: 6 healthy adult sheep., Procedure: In a crossover study, sevoflurane-anesthetized sheep received dexmedetomidine (2 microg/kg, i.v.) without NO (DEX treatment) or with inhaled NO (DEX-NO treatment). Cardiopulmonary variables, including respiratory mechanics, were measured before and for 120 minutes after bolus injection of dexmedetomidine., Results: Dexmedetomidine induced a transient decrease in heart rate and cardiac output. A short-lived increase in mean arterial pressure (MAP) and systemic vascular resistance (SVR) was followed by a significant decrease in MAP and SVR for 90 minutes. Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance increased transiently after dexmedetomidine injection. The Pao2 was significantly decreased 3 minutes after injection and reached a minimum of (mean +/- SEM) 13.3 +/- 78 kPa 10 minutes after injection. The decrease in Pao2 was accompanied by a sudden and prolonged decrease in dynamic compliance and a significant increase in airway resistance, shunt fraction, and alveolar dead space. Peak changes in MPAP did not differ between the 2 treatments. For the DEX-NO treatment, Pao2 was significantly lower and the shunt fraction significantly higher than for the DEX treatment., Conclusions and Clinical Relevance: Inhalation of NO did not prevent increases in pulmonary arterial pressures induced by i.v. administration of dexmedetomidine. Preemptive inhalation of NO intensified oxygenation impairment, probably through increases in intrapulmonary shunting.