Canine and Feline Cutaneous Mast Cell Tumor: A Comprehensive Review of Treatments and Outcomes.

Mast cell tumor (MCT) or mastocytoma is one of the most frequent malignant cutaneous tumors in the dog, and the second most frequent in the cat. Several mast cell tumor therapeutic approaches have been proposed in the past years for dogs and cats, resulting in very distinct outcomes. The current comprehensive literature review presents a critical approach to the scientific information published about the MCTs treatments and the subsequent prognosis and survival times, in dogs and in cats diagnosed with MCTs. A systematic review of the literature following the Cochrane principles and methodology was performed. The authors resorted to MEDLINE, Scopus, Google Scholar and Web of Science databases to select the 133 publications with evidence-based treatments for MCTs in companion animals. Results of the review suggest that the recommended treatment, prognosis and survival times for dogs and cats with MCTs depends at all times on the clinical staging, histological grade and location of the tumor.

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs.

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer's lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n = 11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.

Effects of acute bleeding followed by hydroxyethyl starch 130/0.4 or a crystalloid on propofol concentrations, cerebral oxygenation, and electroencephalographic and haemodynamic variables in pigs.

Bleeding changes the haemodynamics, compromising organ perfusion. In this study, the effects of bleeding followed by replacement with hydroxyethyl starch 130/0.4 (HES) or lactated Ringer's (LR) on cerebral oxygenation and electroencephalogram-derived parameters were investigated. Twelve young pigs under propofol-remifentanil anaesthesia were bled 30 mL/kg and, after a 20-minute waiting period, volume replacement was performed with HES (GHES; N = 6) or LR (GRL; N = 6). Bleeding caused a decrease of more than 50% in mean arterial pressure (P < 0.01) and a decrease in cerebral oximetry (P = 0.039), bispectral index, and electroencephalogram total power (P = 0.04 and P < 0.01, resp.), while propofol plasma concentrations increased (P < 0.01). Both solutions restored the haemodynamics and cerebral oxygenation similarly and were accompanied by an increase in electroencephalogram total power. No differences between groups were found. However, one hour after the end of the volume replacement, the cardiac output (P = 0.03) and the cerebral oxygenation (P = 0.008) decreased in the GLR and were significantly lower than in GHES (P = 0.02). Volume replacement with HES 130/0.4 was capable of maintaining the cardiac output and cerebral oxygenation during a longer period than LR and caused a decrease in the propofol plasma concentrations.

Evaluation of the Cerebral State Index in Cats under Isoflurane Anaesthesia: Dose-Effect Relationship and Prediction of Clinical Signs.

The performance of the cerebral state index (CSI) in reflecting different levels of isoflurane anaesthesia was evaluated in ten cats subjected to four end-tidal isoflurane concentrations (EtIso), each maintained for 15 minutes (0.8%, 1.2%, 1.6%, or 2.0% EtIso). The CSI, hemodynamic data, ocular reflexes, and eye position were recorded for each EtIso concentration. Pharmacodynamic analysis of CSI with EtIso was performed, as well as prediction probability analysis with a clinical scale based on the eye reflexes. The CSI values showed great variability. Between all parameters, burst suppression ratio showed the better fitting with the sigmoidal concentration-effect model (R (2) = 0.93) followed by CSI (R (2) = 0.82) and electromyographic activity (R (2) = 0.79). EtIso was the variable with better prediction of the clinical scale of anaesthesia (prediction probability value of 0.94). Although the CSI values decrease with increasing isoflurane concentrations, the huge variability in CSI values may be a strong limitation for its use in cats and it seems to be no better than EtIso as a predictor of clinical signs.

The effect of high doses of remifentanil in brain near-infrared spectroscopy and in electroencephalographic parameters in pigs.

OBJECTIVE: To study the effects of a high remifentanil bolus dose on pig's electroencephalographic indices and on brain regional and global oxygenation. STUDY DESIGN: Prospective experimental study. ANIMALS: Twelve healthy Large-White male pigs, age 3 months and weight 26.2 ± 3.6 kg. METHODS: Anaesthesia was induced with intravenous propofol 4 mg kg⁻¹, then maintained with constant rate infusions of propofol (15 mg kg⁻¹ hour⁻¹) and remifentanil (0.3 µg kg⁻¹ minute⁻¹). Following instrumentation, all pigs received a 5 µg kg⁻¹ remifentanil bolus. The responses of jugular venous oxygen saturation, cardiac output and cerebral oxygen saturation to the remifentanil bolus were studied. The Bispectral index, spectral edge frequency 95%, total power, approximate entropy and permutation entropy were also studied. Repeated measures anova and Pearson correlation were used to analyze the effect of remifentanil bolus on these variables until 5 minutes after the bolus. RESULTS: Cardiac output and cerebral oxygen saturation decreased significantly after the remifentanil bolus from 4.6 ± 0.9 to 3.8 ± 1.0 L minute⁻¹ and from 65 ± 6 to 62 ± 1% (p < 0.05), respectively. No significant changes were observed in the jugular venous oxygen saturation (p > 0.05) nor in any of the electroencephalogram derived indices (p > 0.05). Correlation analysis revealed strong positive significant correlations between cerebral oxygen saturation and cardiac output (r = 0.82, p < 0.001) and between cerebral oxygen saturation and approximate entropy (r = 0.65, p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The effect caused by the remifentanil bolus on the brain oxygenation seems to be better reflected by the cerebral oxygen saturation than the jugular venous oxygen saturation. The effect of remifentanil on the electroencephalogram may not be reflected in indices derived from the electroencephalogram, but the potential of the approximate entropy in reflecting changes caused by opioids on the electroencephalogram should be further investigated.

Interaction between hydroxyethyl starch and propofol: computational and laboratorial study.

BACKGROUND: Hydroxyethyl starch (HES) is one of the most used colloids for intravascular volume replacement during anesthesia. AIM: To investigate the existence of a chemical interaction between HES and the anesthetic propofol by in vitro propofol dosing, computational docking, and examination of a complex between propofol and HES by infrared (IR), ultraviolet (UV), and (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy. METHODS: Ten samples with human plasma mixed with HES or lactated Ringers (n = 5 for each fluid) were prepared, and the propofol free fraction was quantified until 50 min, using gas chromatography-mass spectrometry. The docking study was performed between HES and propofol and compared with controls. The binding affinities between HES and the small molecules were evaluated by binding free energy approximation (ΔGb, kJ mol(-1)). The IR, UV, and NMR spectra were measured for propofol, HES, and a mixture of both obtained by the kneading method. RESULTS: Propofol concentrations were significantly lower in the HES samples than in the LR samples (p = .021). The spectroscopic characterization of propofol combined with HES revealed differences in spectra and docking studies reinforced a potential interaction between propofol and HES. CONCLUSIONS: Propofol and HES form a complex with different physical-bio-chemical behavior than the single drugs, which may be an important drug interaction. Further studies should evaluate its clinical effects.

Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs with different target-controlled infusions of propofol.

OBJECTIVE: To evaluate if the cerebral state index (CSI), measured by a Cerebral State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or by estimated propofol plasma concentrations. STUDY DESIGN: Prospective clinical study. ANIMALS: Fourteen mixed breed dogs, weighing 24.5 ± 4.7 kg, scheduled to undergo neutering procedures. METHODS: Dogs were premedicated with 0.05 mg kg(-1) acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment were attached. Anaesthesia was induced with propofol using a target controlled infusion (TCI) to varying plasma propofol targets (PropCp). Following endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic maintenance was with propofol by TCI. A PropCp of 3 µg dL(-1) was set initially, then PropCps were increased in 1 µg dL(-1) steps to 7, 9 and then 11 µg dL(-1). Each PropCp was held constant for a 5 minute period, at the end of which depth of anaesthesia was classified using a previously evaluated scale of 'planes' based on palpebral and corneal reflexes and eye position. Cerebral state index (CSI), burst suppression (BSR) and electromyogram were measured at these time points. The prediction probability (PK) of these variables, or of the PropCp in predicting depth of anaesthesia was calculated. RESULTS: The PKs for predicting anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp, respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and 0.65 respectively. CONCLUSION AND CLINICAL RELEVANCE: The Cerebral State Monitor was able to detect very deep planes of anaesthesia when BSR occurs, but was not able to distinguish between the intermediate anaesthetic planes likely to be used in clinical anaesthesia.

Dogs mean arterial pressure and heart rate responses during high propofol plasma concentrations estimated by a pharmacokinetic model.

Propofol total intravenous anesthesia should provide stability of the cardiovascular system. In this study, mean arterial pressure and heart rate were evaluated in eight healthy dogs anesthetized with increasing rates of propofol. The cerebral state index (CSI) was studied as an additional parameter. Although the estimated propofol plasma concentration reached a maximal value of 15.3 µg ml(-1), no hypotension or bradycardia were observed. Exploration of each animal's data revealed high inter-individual variability regarding mean arterial pressure and heart rate. Considering the logarithmic of the concentration, a moderate depressant effect of propofol on mean arterial pressure was revealed in five dogs but the effect was not followed on heart rate.

EMG contributes to improve Cerebral State Index modeling in dogs anesthesia.

Cerebral State Index (CSI) is a measure of depth of anesthesia (DoA) developed for humans, which is traditionally modeled with the Hill equation and the propofol effect-site concentration (Ce). The CSI has been studied in dogs and showed several limitations related to the interpretation of EEG data. Nevertheless, the CSI has a lot of potential for DoA monitoring in dogs, it just needs to be adjusted for this species. In this work, an adapted CSI model is presented for dogs considering a) both Ce and EMG as inputs and b) a fuzzy logic structure with parameters optimized using the ANFIS method. The new model is compared with traditional Hill model using data from dogs in routine surgery. The results showed no significant impact in the model performance with the change of model structure (Fuzzy instead of Hill). The residuals of the Hill model were significantly correlated with the EMG, indicating that the latter should be considered in the model. In fact, the EMG introduction in CSI model significantly decreased the modeling error: 11.8 [8.6; 15.2] (fuzzy logic) versus 20.9 [16.4; 29.0] (Hill). This work shows that CSI modeling in dogs can be improved using the current human anesthesia set-up, once the EMG signal is acquired simultaneously with the CSI index. However, it does not invalidate the search of new DoA indices more adjusted to use in dog's anesthesia.

Remifentanil bolus dose is a safe procedure to control intense noxious stimuli in hypertensive neurosurgical patients.

BACKGROUND: Patients with hypertension may be more prone to develop hypotension as a consequence of opioid administration under general anesthesia. The hemodynamic and bispectral index responses to a remifentanil bolus in neurosurgical hypertensive patients under target-controlled infusion with propofol and remifentanil are addressed. MATERIAL/METHODS: Ten healthy patients and 10 patients with diagnosed hypertension under pharmacological treatment were studied. A 2 microg/kg remifentanil bolus was administered to all patients before skin incision under target-controlled infusion with propofol and remifentanil. Mean arterial pressure, heart rate, and the area under the curve for the bispectral index of the electroencephalogram were analyzed within the groups and compared between them every 30 seconds for two minutes following the bolus. RESULTS: Two minutes after the remifentanil bolus, remifentanil predicted effect-site concentrations reached maximum values of 8.46+/-0.91 ng/ml and 9.74+/-1.29 ng/ml in the healthy and hypertensive patients, respectively. Both groups showed a significant decrease in mean arterial pressure, heart rate, and in the area under the curve for the bispectral index. Mean arterial pressure decreased by 17.3+/-10% and 24+/-9%, heart rate by 11.1+/-8% and 12+/-8%, and the bispectral index by 13+/-9.2% and 8.6+/-8.4% in the healthy and hypertensive patients, respectively, 120 seconds after the remifentanil bolus. CONCLUSIONS: In a clinical situation in which high remifentanil doses may be required, hypertensive patients are expected to have hemodynamic and bispectral index responses similar to those observed in healthy patients.

Individual effect-site concentrations of propofol at return of consciousness are related to the concentrations at loss of consciousness and age in neurosurgical patients.

STUDY OBJECTIVE: To investigate whether a patient's propofol effect-site concentration at return to consciousness (ROC) was related to the propofol effect-site concentration at loss of consciousness (LOC) and to patients' individual demographic parameters. DESIGN: Prospective study. SETTING: Operating room. PATIENTS: 31 ASA physical status I and II neurosurgical patients with Glasgow Coma Score > 15, and scheduled to receive total intravenous anesthesia with effect-site target controlled infusion (TCI) of propofol and remifentanil. INTERVENTIONS: A constant propofol infusion was administered until LOC. At LOC, remifentanil started with a plasma concentration target of 2.5 ng mL(-1). MAIN RESULTS: Propofol concentration at LOC was 4.9 +/- 1 microg mL(-1). At ROC, propofol and remifentanil concentrations were 1.16 +/- 0.3 microg mL(-1) and 3.41 +/- 1.5 ng mL(-1). Significant correlation was observed between propofol concentrations at ROC and LOC, between propofol concentration at ROC and patient age (48.7 +/- 15 yrs), and between propofol concentrations at ROC and LOC, divided by patient's age. CONCLUSIONS: The correlation between propofol concentrations at ROC and LOC was improved by inclusion of patient age data.

Brain tumors may alter the relationship between bispectral index values and propofol concentrations during induction of anesthesia.

STUDY OBJECTIVE: To compare propofol-predicted effect-site concentrations (PropCe) and bispectral index (BIS) of the electroencephalogram during induction of anesthesia in patients with small brain tumors and to analyze BIS and PropCe at loss of consciousness (LOC). DESIGN: Prospective investigation. SETTING: Operating theater of a university hospital. PATIENTS: 26 ASA physical status I and II patients, 13 of whom were scheduled for nontumor spinal surgeries, and the other 13, for brain surgery for small brain tumor removal. INTERVENTIONS: Anesthesia was induced with a propofol 1% constant infusion rate of 200 mL/h until LOC. MEASUREMENTS: BIS, PropCe, heart rate, and mean arterial pressure were analyzed at the beginning of the propofol infusion and every 30 seconds during induction. MAIN RESULTS: The BIS values were significantly higher in patients with brain tumors in the period from 150 to 210 seconds, with PropCe similar to patients without brain tumors. Loss of consciousness occurred 3.6 +/- 0.8 minutes in patients without brain tumors and 3.9 +/- 0.7 minutes in patients with brain tumors. No differences were observed between groups in the time to LOC (3.6 +/- 0.8 in group 1 vs 3.9 +/- 0.7 in group 2) or in BIS at LOC (48.7 +/- 11.4 in group 1 vs 58.6 +/- 21.7 in group 2). CONCLUSIONS: For similar propofol concentrations, patients with small brain tumors show higher BIS values on induction of anesthesia with propofol.

Brain monitoring in dogs using the cerebral state index during the induction of anaesthesia via target-controlled infusion of propofol.

The aim of this study was to evaluate the correlation between the cerebral state index (CSI) and the estimated propofol plasma concentrations in dogs during induction of anaesthesia. Fifteen healthy dogs undergoing scheduled routine surgical procedures were enrolled in this study. Target controlled infusion (TCI) software, based on the pharmacokinetic model for propofol, was used to control the syringe pump and to estimate plasma propofol concentrations (PropCp) and the CSI values every five-seconds. Three electrodes placed in the centre of the forehead, on the left side of the forehead and on the left mastoid were used to collect the electroencephalographic (EEG) signal converted by the cerebral state monitor into the CSI. The cerebral electrical changes induced by increasing propofol concentrations appear to be detected by CSI monitoring in dogs. The negative correlation between CSI and PropCp demonstrates that the CSI could be used to assess electrical brain activity in dogs during the induction of anaesthesia with propofol.

Synchronization software for automation in anesthesia.

This work presents the development of a software for data acquisition and control (ASYS) on a clinical setup. Similar to the industrial Supervisory Control And Data Acquisition (SCADA) the software assembles a Target Controlled Infusion (TCI) monitoring and supervisory control data in real time from devices in a surgical room. The software is not a full controller since the TCI systems comprehend permanent interaction from the anesthesiologist. Based on pharmacokinetic models, the effect-site and plasma concentrations can be related with the drug dose infused and vice versa. The software determines the infusion rates of the drug which are given as commands to the infusion pumps. This software provides the anesthesiologist with a trustworthy tool for managing a safe and balanced anesthesia. Since it also incorporates the acquisition and display of patients brain signals.

Modeling anesthetic drugs' pharmacodynamic interaction on the bispectral index of the EEG: the influence of heart rate.

The effect of drugs' interaction on the brain signal Bispectral Index (BIS) is of great importance for an anesthesia control drug infusion system. In this study, the objective was to inspect the influence of patient's heart rate on the effect of the drugs on BIS. With this goal, the patient's heart rate was incorporated in an drug interaction model. The model was fitted per patient during anesthesia induction, and tested for prediction under surgery. The results showed that the model with time changing parameters incorporating patient's heart rate has a better performance than a non adjusted model. Three clusters of models were also identified using the fuzzy c-means algorithm. These clusters will help to distinguish between different patients' dynamics.

Nonlinear modeling of cerebral state index in dogs.

The Cerebral State Index (CSI) is an electroencephalogram derived signal representing the depression of central nervous activity produced by anesthetic drugs. In this study, a nonlinear model was developed to describe the CSI tendency during general anesthesia in dogs, by evaluating the effect of the anesthetic drug propofol. The model was based on a compartmental and Hill Equation structure with individually identified parameters. The clinical data of 14 dog surgeries were collected and used for modeling and testing. The model presented good results, following the CSI trend. A model for drug-effect for veterinarian anesthesia is an important step when developing advisory, educational and control systems. The overall aim is to improve animal safety and comfort.

Clinical variables related to propofol effect-site concentrations at recovery of consciousness after neurosurgical procedures.

Target controlled infusion (TCI) systems and computer data acquisition software are increasingly used in anesthesia. It was hypothesized that the use of such systems might allow retrieval of information useful to anticipate the effect-site concentrations of propofol at which patients would recover from anesthesia. The goal of the study was to identify variables related to propofol effect-site concentrations at recovery of consciousness (ROC). Sixteen patients with a Glasgow of 15, ASA 1 or 2, subjected to neurosurgical procedures, received TIVA with TCI propofol and remifentanil. Data were collected every 5 seconds from Datex AS3 and Aspect A200XP (BIS). Effect-site TCI was used for propofol (initial effect target 5.0 microg/ml) and for remifentanil (initial plasma target 2.5 ng/ml). All clinical events were noted. Variables possibly related to propofol effect-site concentration at ROC were selected. Data are expressed as mean +/- SD. Effect-site propofol concentration at ROC was 1.3 +/- 0.5 microg/ml. A positive correlation was found between propofol effect-site concentration at ROC and: age (49.3 +/- 17 years) (P = 0.003); mean remifentanil dose during surgery (0.11 +/- 0.05 microg/kg/min) (P = 0.003); mean propofol dose during surgery (0.12 +/- 0.03 mg/kg/min) (P = 0.046); and remifentanil effect-site concentration at ROC (2.85 +/- 2.06 ng/ml) (P = 0.002). Propofol effect-site concentrations were not correlated with: weight, height, LBM, duration of anesthesia, minimum BIS at induction (30.4 +/- 6.8), time till minimum BIS (4.7 +/- 2.2 min), mean and median BIS during surgery (38.2 +/- 4.5 and 37.8 +/- 5.3). BIS-related variables were not useful as ROC predictors. Only drug variables and age correlated with propofol effect-site concentrations at ROC.