Methylene blue as an adjuvant during cardiopulmonary resuscitation: an experimental study in rats.

INTRODUCTION: Methylene Blue (MB) has been shown to attenuate oxidative, inflammatory, myocardial, and neurological lesions during ischemia-reperfusion and has great potential during cardiac arrest. This study aimed to determine the effects of MB combined with epinephrine during cardiac arrest on myocardial and cerebral lesions. METHOD: Thirty-eight male Wistar rats were randomly assigned to four groups: the sham group (SH, n = 5), and three groups subjected to cardiac arrest (n = 11/group) and treated with EPI 20 µg.kg-1 (EPI), EPI 20 µg.kg-1 + MB 2 mg.kg-1 (EPI + MB), or saline 0.9% 0.2 ml (CTL). Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes, and anoxia was maintained for 5 minutes. Cardiopulmonary Resuscitation (CPR) consisted of medications, ventilation, chest compressions, and defibrillation. After returning to spontaneous circulation, animals were observed for four hours. Blood gas, troponin, oxidative stress, histology, and TUNEL staining measurements were analyzed. Groups were compared using generalized estimating equations. RESULTS: No differences in the Returning of Spontaneous Circulation (ROSC) rate were observed among the groups (EPI: 63%, EPI + MB: 45%, CTL: 40%, p = 0.672). The mean arterial pressure immediately after ROSC was higher in the EPI+MB group than in the CTRL group (CTL: 30.5 [5.8], EPI: 63 [25.5], EPI+MB: 123 [31] mmHg, p = 0.007). Serum troponin levels were high in the CTL group (CTL: 130.1 [333.8], EPI: 3.70 [36.0], EPI + MB: 43.7 [116.31] ng/mL, p < 0.05). CONCLUSION: The coadministration of MB and epinephrine failed to yield enhancements in cardiac or brain lesions in a rodent model of cardiac arrest.

Can a Therapeutic Strategy for Hypotension Improve Cerebral Perfusion and Oxygenation in an Experimental Model of Hemorrhagic Shock and Severe Traumatic Brain Injury?

BACKGROUND: Restoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS. METHODS: Thirty-two pigs weighing 20-30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05. RESULTS: The terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment. CONCLUSIONS: The treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.

TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY.

ABSTRACT: Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 × 10 6 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-κB signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.

Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study.

BACKGROUND: Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. METHODS: Twenty pigs were randomly assigned to Control group (n.ß=.ß10), which received saline solution; or to Sildenafil group (n.ß=.ß10), which received sildenafil orally (100.ßmg). After 30.ßminutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4.ß..g.kg-1.h-1) for 180.ßminutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNF.., IL-1.., IL6, and IL10) and troponin I response. RESULTS: Significant hemodynamic alterations were observed after 30.ßminutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19.ß...ß2.ßmmHg to LPS30 52.ß...ß4.ßmmHg, p.ß<.ß0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411.ß...ß29 to LPS180 334.ß...ß49, p.ß<.ß0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35.ß...ß4.ßmmHg at LPS30, p.ß<.ß0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. CONCLUSION: Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study

Abstract Background Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 µg.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response. Results Significant hemodynamic alterations were observed after 30 minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19 ± 2 mmHg to LPS30 52 ± 4 mmHg, p< 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 ± 29 to LPS180 334 ± 49, p< 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 ± 4 mmHg at LPS30, p< 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats.

Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis.

PURPOSE: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. METHODS: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. RESULTS: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). CONCLUSIONS: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Computed Tomography Assessment of Tidal Lung Overinflation in Domestic Cats Undergoing Pressure-Controlled Mechanical Ventilation During General Anesthesia.

Objective: This study aimed to evaluate lung overinflation at different airway inspiratory pressure levels using computed tomography in cats undergoing general anesthesia. Study Design: Prospective laboratory study. Animals: A group of 17 healthy male cats, aged 1.9-4.5 years and weighing 3.5 ± 0.5 kg. Methods: Seventeen adult male cats were ventilated in pressure-controlled mode with airway pressure stepwise increased from 5 to 15 cmH2O in 2 cmH2O steps every 5 min and then stepwise decreased. The respiratory rate was set at 15 movements per min and end-expiratory pressure at zero (ZEEP). After 5 min in each inspiratory pressure step, a 4 s inspiratory pause was performed to obtain a thoracic juxta-diaphragmatic single slice helical CT image and to collect respiratory mechanics data and an arterial blood sample. Lung parenchyma aeration was defined as overinflated, normally-aerated, poorly-aerated, and non-aerated according to the CT attenuation number (-1,000 to -900 HU, -900 to -500 HU, -500 to -100 HU, and -100 to +100 HU, respectively). Result: At 5 cmH2O airway pressure, tidal volume was 6.7± 2.2 ml kg-1, 2.1% (0.3-6.3%) of the pulmonary parenchyma was overinflated and 84.9% (77.6%-87.6%) was normally inflated. Increases in airway pressure were associated with progressive distention of the lung parenchyma. At 15 cmH2O airway pressure, tidal volume increased to 31.5± 9.9 ml kg-1 (p < 0.001), overinflated pulmonary parenchyma increased to 28.4% (21.2-30.6%) (p < 0.001), while normally inflated parenchyma decreased 57.9% (53.4-62.8%) (p < 0.001). Tidal volume and overinflated lung fraction returned to baseline when airway pressure was decreased. A progressive decrease was observed in arterial carbon dioxide partial pressure (PaCO2) and end-tidal carbon dioxide (ETCO2) when the airway pressures were increased above 9 cmH2O (p < 0.001). The increase in airway pressure promoted an elevation in pH (p < 0.001). Conclusions and Clinical Relevance: Ventilation with 5 and 7 cmH2O of airway pressure prevents overinflation in healthy cats with highly compliant chest walls, despite presenting acidemia by respiratory acidosis. This fact can be controlled by increasing or decreasing respiratory rate and inspiratory time.

Assessment of left ventricle myocardial deformation in a hemorrhagic shock swine model by two-dimensional speckle tracking echocardiography.

BACKGROUND: Trauma-induced secondary cardiac injury has been associated with significant adverse cardiovascular events. Speckle tracking echocardiography is a novel technology that allows an accurate and reproducible cardiac structure and function assessment. We evaluated the left ventricle (LV) myocardial deformation by speckle tracking echocardiography in a hemorrhagic shock (HS) swine model. METHODS: Seven healthy male Landrace pigs were included in this study. Severe HS was reached through three sequentially blood withdraws of 20% of estimated blood volume, and it was maintained for 60 minutes. Volume resuscitation was performed using all precollected blood volume. A 1.8- to 4.2-MHz phased-array transducer was used to acquire the two-dimensional echocardiography images. Strain measurements were obtained semiautomatically by wall motion tracking software. Results are presented as medians and interquartile ranges and compared using Wilcoxon rank-sum test. A p value of <0.05 was considered statistically significant. RESULTS: The median weight was 32 (26.1-33) kg, and the median total blood volume withdrawn was 1,100 (1,080-1,190) mL. During the severe HS period, the median arterial systemic pressure was 39 (36-46) mm Hg, and the cardiac index was 1.7 (1.6-2.0) L/min/m 2 . There was statistically significant absolute decrease in the global longitudinal strain 2 hours postresuscitation comparing with the basal measurements (-9.6% [-10.7 to -8.0%] vs. -7.9% [-8.1 to -7.4%], p = 0.03). There were no statistically significant differences between the basal and 2 hours postresuscitation assessments in the invasive/noninvasive hemodynamic, other two-dimensional echocardiogram (LV ejection fraction, 49.2% [44-54.3%] vs. 53.2% [51.5-55%]; p = 0.09), and circumferential strain (-10.6% [-14.4 to -9.0%] vs. -8.5% [-8.6 to -5.2%], p = 0.06) parameters. CONCLUSION: In this experimental swine model of controlled HS, LV global longitudinal strain analysis accurately characterizes the timing and magnitude of subclinical cardiac dysfunction associated with trauma-induced secondary cardiac injury.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Cyclooxygenases 1 and 2 inhibition and analgesic efficacy of dipyrone at different doses or meloxicam in cats after ovariohysterectomy.

OBJECTIVE: To evaluate the cyclooxygenases (COX) inhibition, adverse effects and analgesic efficacy of dipyrone or meloxicam in cats undergoing elective ovariohysterectomy. STUDY DESIGN: Prospective, blinded, randomized, clinical study. ANIMALS: A total of 30 healthy young cats. METHODS: The cats were randomly assigned to three postoperative groups: D25 (dipyrone 25 mg kg-1 every 24 hours), D12.5 (dipyrone 12.5 mg kg-1 every 12 hours) and M (meloxicam 0.1 mg kg-1 every 24 hours). In the first 24 hours, the drugs were administered intravenously (IV), and then orally for 6 (dipyrone) or 3 days (meloxicam). Prostanoids thromboxane B2 and prostaglandin E2 concentrations served as indicators of COX activity and, with physiological variables and pain and sedation scores, were measured for 24 hours after first analgesic administration. Rescue analgesia (tramadol, 2 mg kg-1 IV) was provided if Glasgow feline composite measure pain scale (CMPS-Feline) ≥5. Laboratory tests included symmetric dimethylarginine and adverse effects were evaluated regularly up to 7 and 10 days after surgery, respectively. Parametric and nonparametric data were analyzed with two-way anova and Kruskal-Wallis tests, respectively (p < 0.05). RESULTS: In the first half hour after analgesic administration, COX-1 activity was close to zero and remained significantly lower than before drug administration for 24 hours in all groups. The inhibition of COX-2 activity was significant for 30 minutes in all groups and up to 4 hours in group M. No alterations in laboratory tests or significant adverse effects were observed. Pain scores and need for rescue analgesia did not differ statistically among groups. CONCLUSIONS: Dipyrone at both doses and meloxicam provided a nonselective inhibition of COX-1 and -2 activities and effective analgesia without causing significant adverse effects or laboratory tests alterations. CLINICAL RELEVANCE: Dipyrone at both doses provides equally effective analgesia without causing adverse effects in cats undergoing ovariohysterectomy.

Transient Pulmonary Artery Hypertension in Holstein Neonate Calves.

The neonatal period is a challenging phase for calves, and during this phase constant adaptations are required. The aim of the present study was to evaluate the invasive hemodynamics with the Swan-Ganz catheter in neonate calves to understand adaptive changes during the first 30 days of life. A prospective and observational study was conducted with 10 Holstein calves. Assessments of the right atrial pressure (RAP), right ventricular pressure (RVP), pulmonary artery pressure (PAP), pulmonary capillary pressure (PW), cardiac output (CO), heart rate (HR), pulmonary vascular resistance (PVR), and blood gas levels were performed. The analyses of PAP, PVR, PW, HR, sO2, and arterial blood gases differed (p < 0.05) between the evaluated periods. Our results indicated transient pulmonary artery hypertension during the process of extrauterine adaptation during the first 30 days of life. This hypertension must be considered as physiological and consequent to the neonatal adaptation process.

Grating Visual Acuity in phakic, aphakic, and pseudophakic Poodles.

OBJECTIVE: To compare the grating visual acuity (VA) measured by visual evoked potentials (VEP) in phakic, aphakic, and pseudophakic Poodles. ANIMALS STUDIED: Thirty-six Poodle dogs aged from 4 to 14 years. PROCEDURES: Animals were allocated into three different groups according to their lens status: phakic group (n = 12), aphakic group (n = 12), and pseudophakic group (n = 12). Grating VA was measured in cycles/degree (cpd) in all animals using the electrodiagnosis system Roland RETIport® in a dark room without using any mydriatic, sedative, or anesthetic drugs. RESULTS: The mean grating VA in the phakic, aphakic, and pseudophakic groups was 5.9 ± 1.0 cpd (20/102-Snellen equivalent), 2.6 ± 0.7 cpd (20/231), and 5.2 ± 1.1 cpd (20/116), respectively. The VA from aphakic eyes was significantly lower when compared to the phakic and pseudophakic eyes (P < .05). There was no significant difference in VA between phakic and pseudophakic eyes. CONCLUSIONS: The VEP is a useful tool for the evaluation of grating visual acuity in canines. The study showed that IOL implantation following phacoemulsification results in improved VA as measured by VEP compared to that of the aphakic eye and resulted in VA that was similar to that of the normal eye.

Ultrasound-guided continuous block of median and ulnar nerves in horses: development of the technique.

OBJECTIVE: To develop a technique for ultrasound-guided continuous median and ulnar peripheral nerve block in horses. STUDY DESIGN: Anatomical and prospective experimental study. ANIMALS: A total of 16 thoracic limbs from horse cadavers and 18 adult horses. METHOD: This study was conducted in three phases. Phase 1: Dissection of median and ulnar nerves in the antebrachial region of two cadaver limbs to identify localizing landmarks. Description of sonoanatomy in 14 cadaver limbs using ultrasound-guided perineural infiltration of a combination of cellulose gel (5 mL), contrast medium (4 mL) and methylene blue (1 mL). Catheters were inserted between the perineural sheath and epineurium in six limbs, followed by computed tomography. Phase 2: Ultrasonographic images of the limbs of 18 healthy horses of different breeds were used to define an acoustic window and optimize the approach to nerves. Phase 3: Two case reports of horses with chronic pain of different etiologies. Catheters were inserted between the epineurium and paraneural sheath of the median and/or ulnar nerves guided by ultrasound, followed by continuous infusion of 0.4% ropivacaine. RESULTS: Information from phase 1 was used to direct needle insertion, solution dispersion and catheter implantation in phase 2, which resulted in 100% technique accuracy. In response to the peripheral nerve block, pain reduction was apparent in the two clinical cases by increased weight bearing in affected limbs and decreased requirement for systemic analgesic medications. No local reactions were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrasound technique allowed real-time visualization of needle, catheter and drug dispersion and resulted in a high success rate for nerve blocks. The horses administered a median and ulnar nerve block exhibited no discomfort or signs of infection at the catheter insertion site. Further studies are warranted to validate the efficacy of this technique.

Applicability of optical coherence tomography in blue-fronted parrots (Amazona aestiva).

OBJECTIVE: Optical coherence tomography (OCT) measurement of adult blue-fronted parrots (Amazona aestiva), free from infectious, inflammatory or neoplastic systemic diseases and from any ophthalmological illness, aim at its characterization, as well as to standardize the examination technique for the species. PROCEDURE: Pupillary dilation was achieved with rocuronium bromide (5 mg/mL) at 0, 2, 15, 17, 30, and 32 minutes. The animals were sedated with midazolam maleate (0.5 mg/kg/IM) and anesthetized with propofol (5.0 mg/kg/IV). Measurements were made to evaluate the thickness of the total retina (TR), sensorineural retinal (SR), and ganglion cell complex (GCC), 2 millimeters (mm) from the pecten toward the fovea. OCT data were compared to measurements of retinal histological slides from enucleated eyes of blue-fronted parrots, scanned in automatic fluorescence microscope and measured with by the VS-ASW® software. RESULTS: Averages of measurements from the 43 retinas evaluated by OCT were TR: 279.40 micrometers (µm), SR: 255.90 µm, and GCC: 138.60 µm, respectively, and the measurements of six retinas using fluorescence microscopy were 260.30 µm for TR, 238.20 µm for SR, and 129.30 µm for GCC, demonstrating a high correlation coefficient between all measurements (r = .8698, P < .0001). It is also possible to evaluate the anatomy of the retina and to identify its layers, variations and abnormalities using OCT images. Variations were found between the different areas of the retina, both in the images of the histological slides and in the images of the OCT. CONCLUSION: Optical coherence tomography is a valuable technique for in vivo evaluation of retinal structures in blue-front parrots, providing detailed and accurate images. This method improves the understanding of retinal diseases, monitoring the beginning, progression and therapy of retinal diseases, in the same individuals during longitudinal studies. In comparison to histological investigations, OCT enables imaging in vivo, therefore reducing the number of euthanized animals or enucleated eyes.

Nebulization of Vancomycin Provides Higher Lung Tissue Concentrations than Intravenous Administration in Ventilated Female Piglets with Healthy Lungs.

BACKGROUND: Intravenous vancomycin is used to treat ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus, but achieves high rates of failure. Vancomycin nebulization may be efficient to provide high vancomycin lung tissue concentrations. The aim of this study was to compare lung tissue and serum concentrations of vancomycin administered intravenously and by aerosol in mechanically ventilated and anesthetized healthy piglets. METHODS: Twelve female piglets received a single intravenous dose of vancomycin (15 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of administration. Twelve piglets received a single nebulized dose of vancomycin (37.5 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of the aerosol administration. In each group, vancomycin lung tissue concentrations were assessed on postmortem lung specimens using high-performance liquid chromatography. Blood samples were collected for serum vancomycin concentration measurement 30 min and 1, 2, 4, 6, 8, and 12 h after the end of vancomycin administration. Pharmacokinetics was analyzed by nonlinear mixed effect modeling. RESULTS: One hour after vancomycin administration, lung tissue concentrations in the aerosol group were 13 times the concentrations in the intravenous group (median and interquartile range: 161 [71, 301] µg/g versus 12 [4, 42] µg/g; P < 0.0001). Twelve hours after vancomycin administration, lung tissue concentrations in the aerosol group were 63 (23, 119) µg/g and 0 (0, 19) µg/g in the intravenous group (P < 0.0001). A two-compartment weight-scaled allometric model with first-order absorption and elimination best fit serum pharmacokinetics after both routes of administration. Area under the time-concentration curve from 0 to 12 h was lower in the aerosol group in comparison to the intravenous group (56 [8, 70] mg · h · l vs. 121 [103, 149] mg · h · l, P = 0.002). Using a population model, vancomycin bioavailability was 13% (95% CI, 6 to 69; coefficient of variation = 85%) and absorption rate was slow (absorption half life = 0.3 h). CONCLUSIONS: Administration of vancomycin by nebulization resulted in higher lung tissue concentrations than the intravenous route.

Comparison of pulse pressure variation versus echocardiography-derived stroke volume variation for prediction of fluid responsiveness in mechanically ventilated anesthetized dogs.

OBJECTIVE: To evaluate the ability and accuracy of aortic flow velocity-time integral variation (ΔVTI) and peak aortic velocity variation (ΔVpeak) compared with pulse pressure variation (PPV) to predict fluid responsiveness in mechanically ventilated dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of 50 mechanically ventilated dogs with spontaneous hypotension during orthopedic or oncologic surgery. METHODS: Investigations were performed in the surgery room. When mean arterial pressure (MAP) decreased to <65 mmHg, measurements were performed before and after a fluid challenge (lactated Ringer's solution 5 mL kg-1 over 15 minutes). Responders were defined as a change in stroke volume (SV; transesophageal Doppler) ≥15%. Data were analyzed using paired/unpaired t test or Mann-Whitney/Wilcoxon test when appropriate and receiver operating characteristics (ROC) curves; a p value <0.05 was considered statistically significant. RESULTS: After the fluid challenge, 35 (70%) of 50 dogs were responders with significant increases in SV and decreases in PPV; 15 dogs were nonresponders. ΔVTI and ΔVpeak correlated with a 15% increase in SV. The optimum cut-off value for PPV was 15.6% (sensitivity, 88%; specificity, 100%), for ΔVTI was 10.65% (sensitivity, 65%; specificity, 100%) and for ΔVpeak was 10.15% (sensitivity, 80%; specificity, 100%). The area under the ROC curve for PPV was (0.93 ± 0.08) and for ΔVpeak was (0.89 ± 0.09), before fluid challenge. The gray zone area spread from 6.15% to 15.6% for PPV (18 dogs), 2.45% to 10.65% for ΔVTI (22 dogs) and 0.6% to 10.15% for ΔVpeak (25 dogs). CONCLUSIONS: When using mechanical ventilation, ΔVTI and ΔVpeak predicted fluid responsiveness with the same ability as PPV, based on the area under the ROC curve analysis. However, PPV showed great accuracy demonstrated by a narrower gray zone that included fewer individuals. CLINICAL RELEVANCE: ΔVTI and ΔVpeak can be used as indices of fluid responsiveness in anesthetized dogs.

Predictors and their prognostic value for no ROSC and mortality after a non-cardiac surgery intraoperative cardiac arrest: a retrospective cohort study.

Data on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80-0.93]), with a sensitivity and specificity of 78.4% [69.6-86.3%] and 89.3% [80.4-96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792-0.956]), with a sensitivity of 79.3% [65.5-93.1%] and specificity of 86.1 [74.4-95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.

Continuous peritoneal lavage with vacuum peritoneostomy: an experimental study.

OBJECTIVE: Despite advances in diffuse peritonitis treatment protocols, some cases develop unfavorably. With the advent of vacuum therapy, the use of laparostomy to treat peritonitis has gained traction. Another treatment modality is continuous peritoneal lavage. However, maintaining this technique is difficult and has been associated with controversial results. We propose a new model of continuous peritoneal lavage that takes advantage of the features and benefits of vacuum laparostomy. METHOD: Pigs (Landrace and Large White) under general anesthesia were submitted to laparostomy through which a multiperforated tube was placed along each flank and exteriorized in the left and lower right quadrants. A vacuum dressing was applied, and intermittent negative pressure was maintained. Peritoneal dialysis solution (PDS) was then infused through the tubes for 36 hours. The stability of peritoneostomy with intermittent infusion of fluids, the system resistance to obstruction and leakage, water balance, hemodynamic and biochemical parameters were evaluated. Fluid disposition in the abdominal cavity was analyzed through CT. RESULTS: Even when negative pressure was not applied, the dressing maintained the integrity of the system, and there were no leaks or blockage of the catheters during the procedure. The aspirated volume by vacuum laparostomy was similar to the infused volume (9073.5±1496.35 mL versus 10165±235.73 mL, p=0.25), and there were no major changes in hemodynamic or biochemical analysis. According to CT images, 60 ml/kg PDS was sufficient to occupy all intra-abdominal spaces. CONCLUSION: Continuous peritoneal lavage with negative pressure proved to be technically possible and may be an option in the treatment of diffuse peritonitis.

Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18 F-fluorodeoxyglucose-positron emission tomography.

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via 18 F-fluorodeoxyglucose-positron emission tomography. We analyzed the differential effects of the anesthetics on 18 F-fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel-based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel-based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine-xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K1 were reduced in the KX group. Through various methods of 18 F-fluorodeoxyglucose-positron emission tomography quantification, the present study found that anesthesia with the ketamine-xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of 18 F-fluorodeoxyglucose and its Glut1-mediated transport across the brain membranes (K1 ) were decreased in the KX group.