A step towards effect-site target-controlled infusion with propofol in dogs: a k(e0) for propofol.

Target-controlled infusion (TCI) anesthesia using target effect-site concentration rather than plasma concentration provides less drug consumption, safer anesthesia, less undesired side effects and improved animal welfare. The aim of this study was to calculate the constant that converts propofol plasma into effect-site concentration (k(e0)) in dogs, and to implement it in a TCI system and compare it with the effect on the central nervous system (CNS). All dogs were subjected to general anesthesia using propofol. Fourteen dogs were used as the pilot group to calculate k(e0), using the t(peak) method. Fourteen dogs were used as the test group to test and validate the model. RUGLOOP II software was used to drive the propofol syringe pump and to collect data from S/5 Datex monitor and cerebral state monitor. The calculated k(e0) was incorporated in an existing pharmacokinetic model (Beths Model). The relationship between propofol effect site concentrations and anesthetic planes, and propofol plasma and effect-site concentrations was compared using Pearson's correlation analysis. Average t(peak) was 3.1 min resulting in a k(e0) of 0.7230 min(-1). The test group showed a positive correlation between anesthetic planes and propofol effect-site concentration (R = 0.69; P < 0.0001). This study proposes a k(e0) for propofol with results that demonstrated a good adequacy for the pharmacokinetic model and the measured effect. The use of this k(e0) will allow an easier propofol titration according to the anesthetic depth, which may lead to a reduction in propofol consumption and less undesired side effects usually associated to high propofol concentrations in dogs.

Practical aspects of the use of target controlled infusion with remifentanil in neurosurgical patients: predicted cerebral concentrations at intubation, incision and extubation.

Remifentanil has important side effects and it is not easy to know what remifentanil concentrations should be used during different endpoints of anaesthesia. We analyzed the remifentanil predicted effect-site concentrations (RemiCe) at different events during neurosurgical procedures and assessed if the concentrations used were clinically adequate. BIS and haemodynamic parameters were collected every 5 seconds. Predicted cerebral concentration of propofol (PropCe) and RemiCe were analyzed immediately prior to respective stimulus, and 30, 60 and 90 seconds after. RemiCe were 2.2 +/- 0.3, 6 +/- 2.6 and 2.2 +/- 0.9 ng ml(-1) at intubation, incision and extubation, respectively. PropCe observed in the same periods were 5 +/- 1, 2.6 +/- 0.9 and 1 +/- 0.3 microg ml(-1), also respectively. The remifentanil concentrations used in our patients were lower than reported concentrations, while being clinically adequate to minimize the haemodynamic response to stimulation.

[Hydroxyethyl starch 130/0.4 can be useful to prevent a hemodynamic response to a single dose of remifentanil]. / E1 hidroxietilalmidón (HES) 130/0.4 puede ser úitil en la prevención de la respuesta hemodinámica a un bolus de remifentanilo.

Intravenous propofol and remifentanil are often used in anesthesia. The combined use of these drugs tends to cause hemodynamic depression. We describe the absence of hemodynamic effects in response to infusion of propofol and remifentanil when hydroxyethyl starch (HES) 130/0.4 was also administered. During induction, because blood volume needed to be replaced, two patients aged 62 and 65 years received intravenous HES 130/0.4. They then received a single dose of 2 microg x kg(-1) of remifentanil during total intravenous anesthesia (TIVA) with propofol and remifentanil before placement of a Mayfield head holder. No changes in mean blood pressure or heart rate were observed in either patient after the remifentanil bolus when they have received HES 130/0.4 during TIVA with propofol and remifentanil HES 130/0.4 may play an active role in preventing a hemodynamic response to remifentanil bolus. This hypothesis should be tested in a randomized controlled trial.

Deceased-donor Kidney Transplantation: Predictive Factors and Impact on Postoperative Outcome.

Kidney transplantation (KT) is the treatment of choice in end stage renal disease. Patients proposed for KT have multiple comorbidities, which makes KT a challenge. Our aim was to assess predictive factors for postoperative complications in deceased-donor KT. For data statistical analysis, logistic and linear regressions were used. Between 2012 and 2013, 113 KTs were performed in patients with a mean age 49.9 years. The most prevalent etiology was unknown (32.7%). All patients were in kidney replacement therapy (KRT), for an average of 5.7 years. Most had comorbidities before KT (84.1%), the most frequent hypertension (82.3%). Mean ischemia time (IT) was 1056 minutes. Complications occurred in 93.8% of cases. There were reinterventions in 12.4% of cases, and reinterventions in 13.3%. The time in KRT, IT, and ischemic heart disease had predictive power for the length of hospital stay. Diabetes mellitus before KT and IT were predictors for nephrourologic complications; anemia before KT for hematologic complications; and anemia before KT and time in KRT for cardiovascular complications. The morbidity associated with this disease points to the need to identify and improve the patient-dependent variables influencing its outcome, so as to improve short-term success.

Living-donor Kidney Transplantation: Predictive Factors and Impact on Post-transplant Outcome.

Renal transplantation from living donors represents a valuable opportunity for patients with end-stage renal disease due to short- and long-term outcomes. Nevertheless, it requires that a detailed set of conditions be considered for donor and recipient selection, with possible implications arising from these criteria in the post-transplant outcome. The present work aims to study demographic and clinical characteristics of donors and kidney recipients that predict post-transplantation outcomes after living donor kidney transplantation. With this aim, all patients who underwent donor nephrectomy and living donor transplantation between January 2012 and December 2013 were selected. Demographics, medical comorbidities, and postoperative outcomes were transcribed from electronic patient records. Linear and logistic regressions were applied for data analysis. The study sample consists of 40 patients who underwent living donor kidney transplantation. The presence of peripheral arterial disease and the etiology of end-stage renal disease were the only pretransplant variables that seem to independently predict hospitalization time. Simultaneously, the occurrence of urorenal and infectious complications had a statistically significant correlation with hospitalization time. Additionally, the incidence of cardiovascular complications was correlated with surgical reinterventions at a significant level. The results suggest that careful selection of the donor and the kidney recipient appears to be a prerequisite for a successful transplantation in vivo.

Living-donor and Deceased-donor Renal Transplantation: Differences in Early Outcome--A Single-center Experience.

Living-donor renal transplant (LDRT) yields better long-term outcomes than cadaver-donor renal transplant (CDRT). The aim of the present study was to identify the differences in the early postoperative period between LDRT and CDRT recipients. A retrospective study was conducted including all patients receiving a LDRT and CDRT in this center in 2012 and 2013. A total of 153 recipients were identified (CDRT n = 113, LDRT n = 40). On average, LDRT recipients were younger by 12.7 years (P < .001) and had fewer comorbidities (P < .05). There were no differences in gender or primary kidney disease. Mean time on dialysis, dialytic technique, and ischemia time were different between groups (P < .001, P < .01, P < .001, respectively). On average the length of hospital stay for LDRT recipients was 7 days shorter (P < .001). We found significant differences in the occurrence of early complications (P < .001) and its subtypes, with the exception of neurologic and respiratory complications. There were no differences in reinterventions and readmissions between groups. Recipients' age was an independent risk factor for overall postoperative complications and infectious complications; hypertension before renal transplant and cold ischemia time were predictors for cardiovascular complications; and cold ischemia time also was a predictor of nephrourologic and endocrine complications. CDRT patients had more postoperative complications during hospital stay. The variables identified as predictors of early outcome were different for the 2 groups of patients. Modifiable risk factors for better early outcomes and the impact of immediate complications in long-term graft survival must be investigated.

[Demographic and spatial aspects of scorpion stings in the northwest region of Belo Horizonte City, Minas Gerais, 1993-1996]. / Aspectos demográficos e espaciais dos acidentes escorpiônicos no Distrito Sanitário Noroeste, Município de Belo Horizonte, Minas Gerais, 1993 a 1996.

This paper analyzes a total of 352 scorpion sting reports in the Northwest quarter of Belo Horizonte, Minas Gerais. Traditionally, this area has shown one of the highest case incidence rates, and the present study pointed to 10.37 stings per 10,000 inhabitants. No gender preference was observed, but most victims were 50 years of age or older. Likewise, no relationship was observed between seasonality and sting rates. According to geographic distribution analyses, the highest incidence rates were in areas with the largest scorpion populations. This preliminary descriptive evaluation is important for guidelines to prevent scorpion stings, which should obviously consider local epidemiological features.

Electroencephalogram-based indices applied to dogs' depth of anaesthesia monitoring.

Hypnotic drug administration causes alterations in the electroencephalogram (EEG) in a dose-dependent manner. These changes cannot be identified easily in the raw EEG, therefore EEG based indices were adopted for assessing depth of anaesthesia (DoA). This study examines several indices for estimating dogs' DoA. Data (EEG, clinical end-points) were collected from 8 dogs anaesthetized with propofol. EEG was initially collected without propofol. Then, 100 ml h⁻¹ (1000 mg h⁻¹) of propofol 1% infusion rate was administered until a deep anaesthetic stage was reached. The infusion rate was temporarily increased to 200 ml h⁻¹ (2000 mg h⁻¹) to achieve 80% of burst suppression. The index performance was accessed by correlation coefficient with the propofol concentrations, and prediction probability with the anaesthetic clinical end-points. The temporal entropy and the averaged instantaneous frequency were the best indices because they exhibit: (a) strong correlations with propofol concentrations, (b) high probabilities of predicting anaesthesia clinical end-points.

Fuzzy logic model to describe anesthetic effect and muscular influence on EEG Cerebral State Index.

The well-known Cerebral State Index (CSI) quantifies depth of anesthesia and is traditionally modeled with Hill equation and propofol effect-site concentration (Ce). This work brings out two novelties: introduction of electromyogram (EMG) and use of fuzzy logic models with ANFIS optimized parameters. The data were collected from dogs (n=27) during routine surgery considering two propofol administration protocols: constant infusion (G1, n=14) and bolus (G2, n=13). The median modeling error of the fuzzy logic model with Ce and EMG was lower or similar than that of the Hill with Ce (p=0.012-G1, p=0.522-G2). Furthermore, there was no significant performance impact due to model structure alteration (p=0.288-G1, p=0.330-G2) and EMG introduction increased or maintained the performance (p=0.036-G1, p=0.798-G2). Therefore, the new model can achieve higher performance than Hill model, mostly due to EMG information and not due to changes in the model structure. In conclusion, the fuzzy models adequately describe CSI data with advantages over traditional Hill models.

The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anaesthetized patients independently from intubation and surgical stimuli.

BACKGROUND AND OBJECTIVE: Remifentanil boluses are used in different clinical situations and the effects on bispectral index monitoring are unclear. We analysed the effect of a remifentanil bolus on the bispectral index of the electroencephalogram (bispectral index) under total intravenous anaesthesia with propofol and remifentanil. METHODS: ASA I-III patients were included in this study. All patients received a 2 microg k g-1 remifentanil bolus in a period free from stimuli. Bispectral index and haemodynamic data were collected from an A-2000XP bispectral index monitor (every second) and an AS/3 Datex monitor (every 5 s). Bispectral index data were analysed using the area under the curve. Mean arterial pressure and heart rate were averaged at each 30-s period and analysed using analysis of variance. RESULTS: A total of 240 bispectral index values were obtained per patient. The area under the curve between 90 and 120 s after the bolus was significantly lower than the basal area under the curve (average of all areas before the bolus, P < 0.05). Mean arterial pressure and heart rate were significantly reduced from 96.4 +/- 19.9 mmHg at the time of the bolus to 74.2 +/- 16.6 mmHg 120 s after, and from 70 +/- 16.4 bpm at the time of the bolus to 61 +/- 13.6 bpm after (P < 0.001), respectively. CONCLUSIONS: There was a significant reduction in the areas under the curve between 90-120 s following the bolus. Heart rate and blood pressure also showed significant reductions. Thus, remifentanil bolus given under total intravenous anaesthesia with propofol and remifentanil decreases bispectral index, an effect independent of intubation and surgical stimuli.

Pancreatic size and enzyme contents after vagal deafferentation in jejunectomised pigs under free or restricted feeding.

A factorial experiment was designed to test under different feeding levels the effects of the surgical deprivation of sensory afferences (deafferentation) arising from the gastrointestinal tract, including the intestinal chemosensitivity, on the jejunectomised pig used as a model. Within 28 days, the limited jejunectomy failed to affect the pancreas and the enzyme activities were not affected by the feeding level (within the limit of 70% of ad libitum). It was shown that the deafferentation induced significant reductions in the pancreatic tissue mass and in the various enzyme activities, thus suggesting the possible importance of intestinal sensibility for the pancreas.

Effects of three microbial probiotics on postprandial porto-arterial concentration differences of glucose, galactose and amino-nitrogen in the young pig.

Postprandial kinetics of porto-arterial concentration differences of glucose (G), galactose (Gal), L-lactic acid (LA) and amino-N (AN) were studied in the piglet after the ingestion of 10(7) colony-forming units (cfu) Sporolactobacillus P44 (SP), or 10(6) cfu Bacillus cereus IP5832 (AC), or 10(6) cfu of a combination of Lactobacillus acidophilus, L. fermentum and L. brevis (AB)/g feed. Sixteen fistulated piglets (portal vein and brachiocephalic trunk; mean body weight 22 (SD 2) kg) were used. The diet was based on skimmed milk (320 g/kg), barley (300 g/kg), wheat bran (110 g/kg), maize (100 g/kg) and lactose (70 g/kg). The postprandial blood kinetics, four measurements per animal at 1-week intervals, were studied for 6 h after the ingestion of test meals of 400 g basal diet (BD) or this diet supplemented with the bacteria (SP, AC and AB respectively). Areas of porto-arterial concentration differences (APACD) of G, Gal and LA were not influenced by the bacteria supplements. APACD of AN was significantly higher after the ingestion of the SP diet than that estimated for BD.

Effects of guar gum and cellulose on glucose absorption, hormonal release and hepatic metabolism in the pig.

Six Large White pigs (mean body-weight 59 (SE 1.7) kg) were surgically fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein, as well as with electromagnetic flow probes around the portal vein and the hepatic artery, and allowed to recover. The non-anaesthetized animals were given a basal non-fibre diet (diet A) alone or together with 60 g guar gum/kg (diet B) or 150 g purified cellulose/kg (diet C) by substitution for mica. The diets were given for weekly periods and according to a replicated 3 x 3 Latin square design. On the last day of each such adaptation period, test meals of 800 g were given before blood sampling. Sampling was continued for 8 h. Guar gum strongly reduced glucose apparent absorption without changing the absorption and the hepatic uptake profiles. Production rates of insulin, gastric inhibitory polypeptide and insulin-like growth factor-1 (IGF-1) were lowest after guar gum ingestion. However, the reductions in peripheral blood insulin levels caused by guar gum were not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly secreted by the gut, whereas the liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut-produced IGF-1. Guar gum ingestion appeared also to decrease glucagon secretion. Cellulose at the level consumed had very few effects on the variables considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the metabolic effects described.

Pancreatic exocrine secretion in the pig following test meals of different composition and intra-duodenal loads of glucose and maltose.

Eleven pigs were fitted with pancreatic and duodenal fistulae, and pancreatic juice collected permanently. Amylase, chymotrypsin, lipase and total proteins were determined in juice collected within 2 and 6 hours after different test-meals or intraduodenal loads of glucose and maltose. In the pancreatic juice of pigs adapted to a high-lipid diet and submitted to a high-carbohydrate test-meal the activity of amylase was increased by 50%. When the consumption of the high-lipid meal was associated with an intraduodenal load of 100 g of glucose all the enzyme activities were stimulated when compared to the effect of meal alone, but only the activity of amylase was significantly increased (+ 82%). In the juice of pigs adapted to a balanced diet and submitted to intraduodenal loads of 150 ml of water, 50 g of glucose, 50 g of maltose and 150 g of maltose, the enzyme activities remained almost constant with the load of water and 50 g of maltose but with 50 g of glucose and 150 g of maltose loads, amylase activity was increased by 20% and 30% respectively. It is suggested, that the exocrine pancreas of the pig adapts itself rapidly to the changes in the size of the intestinal pool of starch hydrolysis products.

Effects of guar gum on plasma urea, insulin and glucose in the growing pig.

1. Six growing pigs fitted with portal and arterial blood cannulas were given a barley-fishmeal diet, either alone or supplemented with guar gum at 60 g/kg basal diet. Blood samples were taken during 8 h following test meals given at 08.00 hours. 2. Ingestion of the guar-gum-supplemented diet appeared to increase systematically portal and arterial levels of plasma urea. At peak values, 4 and 5 h after the test meal, this effect was statistically significant (P less than 0.05). 3. Irrespective of which diet was given, portal and arterial blood samples, withdrawn at the same time, were found to have about the same concentration of urea. This was found throughout the 8 h studied and implies that no net exchange of urea between the circulation and the gastrointestinal tract, as a whole, took place. 4. In the time-period 30-60 min following the test meal, guar gum significantly reduced the postprandial hyperglycaemia and hyperinsulinaemia in portal blood.

Amino acid absorption and production of pancreatic hormones in non-anaesthetized pigs after duodenal infusions of a milk enzymic hydrolysate or of free amino acids.

1. Six non-anaesthetized pigs (mean body-weight 57.0 kg) were used to study the intestinal absorption of amino acids (AA) from either an enzymic hydrolysate of milk (PEP) containing a large percentage of small peptides (about 50% with less than five AA residues) and very few free AA (8%), or from a mixture of free AA with an identical pattern (AAL) infused intraduodenally in one of two amounts (55 or 110 g). Concomitant insulin and glucagon production rates were estimated. 2. Each pig was previously fitted, under anaesthesia, with an electromagnetic flow probe around the portal vein, with permanent catheters in the portal vein, the carotid artery and the duodenum. Each infusion was performed after an 18 h fasting period and each pig received each infusion. The observation period lasted for 5 h. 3. The absorption of AA was greater, more rapid and more homogeneous after PEP infusion than after AAL infusion, independent of the amount infused. 4. For the majority of AA considered individually, the absorption coefficient was higher after infusion of PEP than after that of AAL. The exceptions were methionine with a higher absorption coefficient after AAL infusion, and isoleucine, aspartic acid + asparagine and glutamic acid + glutamine with identical coefficients for both infusions. 5. Some AA, such as asparagine, ornithine, citrulline and taurine, while absent in the infusates, appeared in the portal vein in appreciable amounts after the infusion of both solutions. While a small proportion of taurine may arise from recycling of taurine-containing bile salts, it seems that the gut wall is able to synthesize all four AA. 6. Insulin production did not differ according to the nature or amount of solutions infused. Glucagon production was greater after PEP infusion.

Radial basis function neural networks versus fuzzy models to predict return of consciousness after general anesthesia.

This work presents two modelling techniques to predict return of consciousness (ROC) after general anaesthesia, considering the effect concentration of the anaesthetic drug at awakening. First, several clinical variables were statistically analysed to determine their correlation with the awakening concentration. The anaesthetic and the analgesic mean dose during surgery, and the age of the patient, proved to have significantly high correlation coefficients. Variables like the mean bispectral index value during surgery, duration of surgery did not present a statistical relation with ROC. Radial basis function (RBF) neural networks were trained relating different sets of clinical values with the anaesthetic drug effect concentration at awakening. Secondly, fuzzy models were built using an adaptive network-based fuzzy inference system (ANFIS) also relating different sets of variables. Clinical data was used to train and test the models. The fuzzy models and RBF neural networks proved to have good prediction properties and balanced results.

Glucose turnover and recycling in unrestrained and unanesthetized 48-h-old fasting or post-absorptive newborn pigs.

The metabolism of glucose has been studied in 48-h-old unanesthetized fasting and post-absorptive sucking piglets. Both [6-3H]- and [U-14C]glucose were administered either by a single injection method or by a primed infusion technique. The rates of glucose turnover and recycling were estimated under steady-state conditions. The rates of glucose turnover and recycling in 48-h-old fasting or post-absorptive piglets were not statistically different when measured using the single injection technique or the primed infusion method. The mean (with SE) rate of glucose turnover was 65.8 (2.5) in post-absorptive and 31.1 (1.9) mumol/kg per min in fasted newborn pigs. Glucose utilization was linearly related to blood glucose concentration; regression analysis indicated a y-intercept of 7.2 mumol/kg per min. As tested by arterio-portal differences the gut was not releasing glucose or galactose in 5 h-post-absorptive sucking newborn pigs. Thus, the higher rates of glucose turnover in post-absorptive newborn pigs compared with fasting ones suggest that hepatic glucose production is enhanced in post-absorptive sucking piglets. The mean (with SE) rates of glucose recycling were four times higher in post-absorptive piglets than in fasting ones, i.e. 14.4 (1.6) and 3.7 (0.5)% of [6-3H]glucose turnover respectively. As liver glycogen was exhausted in 48-h-old sucking piglets, this suggests that hepatic glucose production results from gluconeogenesis.

Effects of supplemental phytase on performance and phosphorus utilisation in broiler chickens fed a low phosphorus diet without addition of inorganic phosphates.

1. Three experiments were conducted to evaluate the effects of the dietary addition of fungal phytase (derived from Aspergillus niger) on the performance and phosphorus utilisation in broiler chickens receiving low phosphorus diets without additional inorganic phosphates. 2. Graded amounts of supplemental phytase (125, 250, or 500 PU/kg diet) resulted in significant increases in both growth rate and food intake. However, only moderate improvements in food conversion were noted. 3. The enhancement of chick performance was related to an improved utilisation of dietary phosphorus, as confirmed by significantly elevated plasma concentrations of inorganic phosphorus and increased tibia ash percentages in birds receiving phytase-treated diets. The apparent availability of phosphorus was markedly improved and its concentration in excreta was reduced (experiment 1, P < 0.05). 4. It was concluded that an inclusion of phytase into practical broiler diet will allow the reduction or omission of additional dietary inorganic phosphorus.