Update and evaluation of the egg production model in laying hens.

The egg production model (EPM) described here is a mechanistic and stochastic model that simulates the amino acid and energy requirements of laying hens. It takes into account their potential rate of laying, and egg weight over time, and the composition of the feed provided. The model predicts feed intake based on the assumption that hens will consume enough feed to reach their genetic potential. The environment is assumed to be non-limiting, although feed intake may be constrained by bulk capacity when bulky feeds are offered. The simulation model integrates a least-cost feed formulator, which enables the prediction of a feeding program that maximizes economic returns. A series of simulations were conducted to demonstrate the model behavior, external evaluation, and the economic optimization routine. The model behavior showed that as the energy content in the feed decreased, the simulated feed intake increased to compensate. Consequently, feeds with lower energy concentrations led to an overconsumption of nutrients, resulting in increased egg component weights (yolk and albumen). However, when the balanced protein was reduced while maintaining a constant energy-to-protein ratio, there was no change in egg components, consistent with published literature. The external evaluation indicated that feed intake, egg production, and egg weight were estimated with low error, and there was a similar trend observed between the estimated and observed data. This demonstrates the reliability of the model. Additionally, the paper provides a demonstration of how to use and interpret the results from the egg production model, including the economic optimization routine. The study found that a feed containing 7.8 g/kg of digestible lysine maximized economic returns. This optimization tool can be valuable in making nutritional decisions to optimize economic returns in an egg production system.

Evaluation of a mechanistic model that estimates feed intake, growth and body composition, nutrient requirements, and optimum economic response of broilers.

Efficient meat production is crucial in addressing global market demands and sustainability goals. Modeling production systems has gained worldwide attention, offering valuable insights for predicting outcomes and optimizing economic returns. In the poultry industry, researchers have developed mathematical models to predict animal performance and maximize profits. These models incorporate theories to explain real-world processes and enable future event predictions. One such model is the Broiler Growth Model (BGM), which serves as a predictive tool for estimating feed intake, growth, and body composition of broilers. The BGM takes into account the genetic potential of the broilers, the feed they are provided, and several constraining factors that may prevent the animal from achieving their genetic potential. To evaluate the BGM, a series of simulations were performed: (i) model behavior was evaluated by simulating the response of males and females from 22 to 35 d to feeds differing in dietary protein content and nutrient density; (ii) model prediction was evaluated using the results of a protein response trial conducted at UNESP in which six dietary protein levels were fed to male and female broilers over a 56 d period; and (iii) model optimization was used to maximize economic returns in the above trial. The model behaved as expected when feeds differing in protein content were fed, with feed intake per kg of BW increasing as protein level was decreased, resulting in lower gains and higher body lipid contents. Increasing nutrient density resulted in higher feed intake in the second level, followed by a reduction in feed intake in the highest nutrient feed. The simulated response to nutrient density resulted in increasing body lipid deposition as the nutrient density increased. In comparing the simulated and actual results of the protein response trial, the overall error of prediction was up to 15% for feed intake, BW, and body protein. The optimization routine allows the simulation of different economic scenarios, helping in decision-making. The Broiler Growth Model emerges as a valuable tool for the poultry industry, offering predictive capabilities and economic optimization potential. While minor discrepancies between simulated and actual results exist, the BGM holds significant promise for enhancing efficiency and profitability in broiler production, contributing to the broader goals of sustainable broiler meat production.

A first model of the fate of dietary calcium and phosphorus in broiler chickens.

To reduce P excretion and increase the sustainability of poultry farms, one needs to understand the mechanisms surrounding P metabolism and its close link with Ca metabolism to precisely predict the fate of dietary P and Ca and related requirements for birds. This study describes and evaluates a model developed to estimate the fate of Ca and P consumed by broilers. The Ca and P model relies on three modules: (1) digestion of Ca and P; (2) dynamics of Ca and P in soft tissue and feathers; and (3) dynamics of body ash. Exogenous phytase affects the availability of Ca and P; thus, to predict the absorption of those minerals, the model also accounts for the effect of phytase on Ca and P digestibility. We used a database to estimate the consequences of dietary Ca, P, and phytase over feed intake response. This study followed a four-step process: (1) Ca and P model development and its coupling with a growth broiler model; (2) model behavior assessment; (3) sensitivity analysis to identify the most influential parameters; and (4) external evaluation based on three databases. The proportion of P in body protein and the Ca to P ratio in bone are the most sensitive parameters of P deposition in soft tissue and bone, representing 91 and 99% of the total variation. The external evaluation results indicated that body water and protein had an overall mean square prediction error (rMSPE) of 7.22 and 12.3%, respectively. The prediction of body ash, Ca, and P had an rMSPE of 7.74, 11.0, and 6.56%, respectively, mostly errors of disturbances (72.5, 51.6, and 90.7%, respectively). The rMSPE for P balance was 13.3, 18.4, and 22.8%, respectively, for P retention, excretion, and retention coefficient, with respective errors due to disturbances of 69.1, 99.9, and 51.3%. We demonstrated a mechanistic model approach to predict the dietary effects of Ca and P on broiler chicken responses with low error, including detailed simulations to show the confidence level expected from the model outputs. Overall, this model predicts broilers' response to dietary Ca and P. The model could aid calculations to minimize P excretion and reduce the impact of broiler production on the environment. A model inversion is ongoing that will enable the calculation of Ca and P dietary quantities for a specific objective. This will simplify the use of the model and the feed formulation process.

Eimeria maxima infection impacts the protein utilisation of broiler chicks from 14 to 28 days of age.

In floor-raised broilers, coccidiosis is responsible for reducing the use of nutrients, mainly by impairing intestinal tissue function and activating the immune system. Understanding and quantifying how balanced dietary protein (BP) is used when birds are challenged will allow nutritionists to make decisions regarding challenged flocks. This study aimed to determine the effects of Eimeria maxima on broiler performance and body composition, and to calculate changes in the maintenance and efficiency of protein utilisation (Ep). A total of 2 400 male 14-day-old Cobb500 broiler chickens were randomly allotted to ten groups with six replications of 40 birds each, with a 5 × 2 factorial arrangement of treatments. Five levels of BP in reference to digestible lysine (3.6, 7.2, 10.8, 14.4, and 18.0 g/kg) were fed to unchallenged (NCH) and challenged (CH) broilers with 7 × 103E. maxima sporulated oocysts from 14 to 28 days of age. Performance and body deposition were measured using a comparative slaughter technique to compare BP maintenance requirements and Ep. ANOVA followed by a posthoc test was performed to compare the effects of BP levels, challenge, and their interactions. A monomolecular model describing the responses of NCH and CH broilers to BP intake, maintenance, and maximum protein deposition was compared. There were significant interactions between body weight gain and digestible lysine intake among the factors studied. Infection had a negative impact on all variables analysed, proving the efficacy of the challenge. The maintenance did not differ between the CH and NCH groups. Increased levels of dietary BP did not recover the maximum protein deposition in CH broilers. Eimeria maxima significantly reduced Ep by a factor of 0.09 times on Ep compared to the control group. The Eimeria maxima challenge was responsible to modify the use of BP altering the body composition and impairing broilers performance.

Energy cost of physical activities in growing broilers.

1. The time-energy budget method estimates the energy used for physical activity (PA) by integrating behaviour PA patterns with energy cost for specific PAs. Nevertheless, information about individual energy cost by type of PA are not available and so this study estimated the energy cost of PA for growing broilers.2. An indirect calorimetry system for single birds was constructed to measure the variation in the rate of O2 consumption (V˙O2, L/min) and rate of CO2 production (V˙CO2, L/min) produced by these PAs.3. A total of five birds were used in a replicated trial where their body weight (BW) ranged from 1.5 to 2.5 kg to measure the increase in heat production (HP) above resting levels as a result of PA. The procedure in the chamber was divided into five steps: (1) initial baselining, (2) resting metabolic rate, (3) PA such as feeding, drinking and other standing activities, (4) removal of gas exchange produced in step 3, and (5) final baselining. The PA was recorded using a video camera fixed at the chamber's top (and outside).4. The area under V˙CO2 and V˙O2 curves was used to calculate the CO2 production (vCO2, L) and O2 consumption (vO2, L). Then, the HP (cal/kg-0.75) was calculated according to the Brouwer equation. Two observers analysed the video records to estimate the time spent for each PA (seconds and frequency).5. To calculate the energetic coefficients, the HP was regressed with the function of time spent to perform each PA allowing to estimate the energy cost for eating, drinking and stand activities, which were 0.607, 0.352 and 0.938 cal/kg-0.75/s, respectively.

Gut capacity of broiler breeder hens.

1. Broiler breeders are subjected to qualitative or quantitative feed restrictions to prevent obesity, which causes major health and welfare problems. Diluting their feed by adding inert or low nutrient, bulky materials can reduce obesity, but the capacity of the gut needs to be determined to apply this strategy successfully. Two trials were conducted to measure the bulk capacity of Ross 308 broiler breeders prior to and after the onset of lay. The trial was completely randomised, with nine individually-caged breeders, with each cage as a replicate, totalling 189 birds per trial2. Birds were given ad libitum access to one of 21 maize-soyabean based feeds, an undiluted control or progressive dilution (10, 20, 30 and 40%) with either cellulose fibre, rice husk, sand, vermiculite or sawdust. Feeds were analysed for density, crude-, acid detergent- and neutral detergent-fibre, water-holding capacity (WHC), cation-exchange capacity and oil-holding capacity.2. In general, feed intake (scaled to body weight0.67) increased and then declined as the proportion of each diluent increased. Intake increased linearly when rice hulls and sand were used as diluents.3. Water holding capacity was the most appropriate measure to define the gut capacity of broiler breeders.4. The trial data was used to estimate the maximum-scaled feed intake (SFImax) in broiler breeders, which was 240-56.1WHC + 4.34WHC2 g/kg0.67/d.

The response of reproducing Japanese quail to dietary valine.

1. A feeding trial was conducted to measure the responses of Japanese quail to dietary valine. In total, 280 Japanese quail were randomly assigned to eight treatments giving seven replicates (cage - 35 cm length, 35 cm width × 15 cm high). Experimental diets were formulated using a dilution technique to give a range dietary Val concentration (1.97 to 9.85 g/kg).2. Feed intake was maximised at 6.66 g Val/kg and above, but declined linearly below this level. Body weight reached a maximum of 170 g on 6.66 g Val/kg. Egg output peaked at 9.5 ± 0.3 g/bird/d with an egg weight of 11 g for the 6.66 g Val/kg diet. Rate of laying for the group that received the feed with the lowest Val content was close to zero (1.40%), but egg weight on this treatment was 70% of the maximum egg weight. Valine required per gram of egg output was estimated as 10.6 mg/g, whereas the maintenance requirement was 159 mg/kg body weight. Val required for maximum egg output was estimated in 154 mg/d.3. The marginal cost of Val in Brazil currently is negative below a level of 8.0 g/kg feed, which is above that required for maximum egg output. Consequently, Val cannot be regarded as a limiting amino acid currently, as the optimum economic intake exceeds the requirements of all the individuals in the population. The price of a quail egg weighing 11 g in Brazil at the time of the experiment was R$ 0.021. Even if the marginal revenue for these eggs was doubled to 0.4 c/g, there would be no reason to increase the intake of Val.

Mycobacterium avium subspecies paratuberculosis and bovine leukemia virus seroprevalence and associated risk factors in dairy herds in Minas Gerais state, Brazil / [Soroprevalência do Mycobacterium avium subespécie paratuberculosis e vírus da leucemia bovina e fatores de risco associados em rebanhos leiteiros de Minas Gerais, Brasil]

Mycobacterium avium subesp. paratuberculosis (MAP) e o vírus da leucemia bovina (BLV) são agentes que causam grandes perdas econômicas nos rebanhos. O objetivo deste estudo foi avaliar a situação epidemiológica da paratuberculose bovina (PTB) e leucose enzoótica bovina (EBL) em rebanhos leiteiros de Lagoa Formosa, Minas Gerais, Brasil. Foram coletadas 236 amostras de sangue de vacas, as quais foram submetidas aos testes ELISA e imunodifusão em gel de ágar para detecção de anticorpos contra MAP e BLV. A soroprevalência de anticorpos contra MAP e BVL foi de 20% para os rebanhos e 6% para os animais e de 85% para os rebanhos e 50,42% para os animais, respectivamente. A presença dessas enfermidades deve servir como um alerta para os produtores e veterinários, para que concentrem maior atenção na implementação de medidas higiênico-sanitárias, incorporando elementos de vigilância com base nos riscos identificados no estudo.(AU)

Fisetin as a promising antifungal agent against Cryptocococcus neoformans species complex.

AIMS: The aim of this study was to investigate the mechanisms of action of fisetin, a flavonol with antifungal activity previously evaluated against the Cryptococcus neoformans species complex. METHODS AND RESULTS: Ergosterol content and flow cytometry analysis were determined for the C. neoformans species complex in the presence of fisetin and ultrastructural analysis of morphology was performed on Cryptococcus gattii and C. neoformans. Decrease in the total cellular ergosterol content after exposure to fisetin ranged from 25·4% after exposure to 128 µg ml(-1) to 21·6% after exposure to 64 µg ml(-1) of fisetin compared with the control (without fisetin). The fisetin effects obtained with flow cytometry showed metabolic impairment, and alterations in its normal morphology caused by fisetin in C. neoformans cells were verified using scanning electron microscopy. CONCLUSIONS: Fisetin is a compound that acts in the biosynthesis of ergosterol. Flow cytometry showed that fisetin reduced viability of the metabolically active cells of C. gattii, while morphological changes explain the action of fisetin in inhibiting growth of these fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study supports the idea that fisetin may represent a good starting point for the development of future therapeutic substances for cryptococcosis.

Liquid chromatography/negative electrospray ionization ion trap MS(2) mass spectrometry application for the determination of microcystins occurrence in Southern Portugal water reservoirs.

Microcystins (MCs) are toxins produced by cyanobacteria which are common organisms in the phytoplankton of eutrophic lakes, rivers and freshwater reservoirs. In the present work, a novel method of liquid chromatography-electrospray ion trap tandem mass spectrometry (LC/ESI/Ion trap-MS/MS), operated in the negative ionization mode, was developed for the analysis of these cyanotoxins. The method was applied to determine the amounts of total microcystins-LR, -YR and -RR in two water reservoirs in Southern Portugal, namely Alqueva and Beliche. A total of 30 water samples were analysed along 2011. Solid phase extraction (SPE) was used for sample cleaning-up and analyte enrichment. The extracted toxins were separated on a C18 column with a gradient of acetonitrile/water with 0.1% formic acid. Detection of microcystins was carried out using multiple reaction monitoring (MRM) in the negative polarity mode, as this method gave a higher selectivity. The MC-RR, YR and LR quantification limits were 17.9, 31.7 and 15.8 ng/L, respectively; quite below the limits recommended by WHO guidelines for drinking water (1 µg/L). Total MC highest concentrations were found in the warm months of June, July and September in Alqueva sampling sites, with concentrations of MC LR and RR ranging 17-344 and 25-212 ng/L, respectively, showing comparable results for MC-RR and LR and slightly lower concentration of MC-YR. Detected values for Beliche reservoir were below quantification limits.

Altos níveis de fitase em rações para frangos de corte / High levels of phytase in diets for broilers

Avaliaram-se o desempenho, o coeficiente de digestibilidade da matéria seca (CDMS), da proteína bruta (CDPB), a retenção aparente de cálcio (Ca) e fósforo (P) e a energia metabolizável aparente corrigida para balanço de nitrogênio (EMAn) de dietas suplementadas com altos teores de fitase (FTU) para frangos, até 35 dias de idade. Foram utilizados 1848 pintos, distribuídos em delineamento inteiramente ao acaso, com sete tratamentos e oito repetições de 35 aves. Os tratamentos foram: T1: dieta-controle; T2: dieta com inclusão de 1.500FTU/kg; T3: 3.000FTU/kg; T4: 4.500FTU/kg; T5: 6.000FTU/kg; T6: 8.000FTU/kg e T7: 10.000FTU/kg de ração. No 10º e 28º dias de experimento, quatro e três aves, respectivamente, foram transferidas para gaiolas de metabolismo. A partir da inclusão de 4.500FTU/kg, o desempenho das aves de 1 a 35 dias foi semelhante ao das aves do grupo-controle (P>0,05). Não houve diferença (P>0,05) entre os tratamentos nos CDPB e nos valores de EMAn, porém, na fase inicial, observou-se maior aproveitamento da MS com os altos níveis de fitase (P<0,05). Em relação à retenção de Ca e P, houve efeito positivo da suplementação enzimática, com aumento significativo do uso desses minerais pelas aves. Concluiu-se que é possível suplementar altos teores de fitase valorando adequadamente os nutrientes da dieta.

The digestibility of dry matter (DMD), and of crude protein (CPD), the apparent retention of calcium (Ca) and phosphorus (P) and apparent metabolizable energy corrected by nitrogen balance (AME) of diets supplemented with high levels of phytase (FTU) for broilers, 35 days old were evaluated. A total of 1848 chicks were distributed in a completely randomized experiment with seven treatments and eight repetitions. The treatments were: T1: control diet, T2: inclusion of 1,500FTU/kg; T3: 3,000FTU/kg; T4: 4,500FTU/kg; T5: 6,000FTU/kg; T6:8,000FTU/kg; and T7: 10,000FTU/kg feed. On the 10th and 28th days of the experiment, four and three birds, respectively, were transferred to metabolism cages. An addition of 4,500FTU/kg from 1 to 35 days resulted in a performance similar to the control group (P>0.05). There was no difference (P>0.05) among treatments for DMD and AME, however, during the initial phase there was a higher use of MS with high levels of phytase (P<0.05). Regarding the retention of Ca and P, a positive effect of enzyme supplementation significantly increased the use of these minerals by birds. It is possible that high levels of supplemental phytase adequate valuing the nutrients.

Molecular characterization of early colonizer bacteria from wastes in a steel plant.

AIMS: Forty-nine bacteria isolated from four newly-produced waste samples of a steel industry, which had a high content of CaO, MgO, Cr and P2O5, were characterized molecularly and phenotypically by susceptibility testing against heavy metals. METHODS AND RESULTS: Phylogenetic analysis using 16S rRNA gene sequences revealed that the isolates belonged to nine genera, Pseudomonas, Micrococcus, Acinetobacter, Bacillus, Dietzia, Kocuria, Diaphorobacter, Staphylococcus and Brevibacillus. Besides, some isolates could be affiliated to species: M. luteus, Ac. junii, Ac. schindleri, B. cereus, K. marina, D. nitroreducens and Staph. warneri. The bacteria that were characterized are taxonomically diverse, and Pseudomonas and Micrococcus predominated. Fingerprinting BOX-PCR revealed high genomic heterogeneity among the isolates. Among the heavy metal compounds Zn, Ni, Pb and Cu were least toxic to the bacterial isolates, whereas Ag inhibited all isolates at 0.001 mmol l(-1). CONCLUSIONS: Heterotrophic bacteria, affiliated with several phylogentic groups, were able to colonize different wastes of a steel industry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study extends our knowledge of the early colonizers bacteria populating siderurgic environments. Some of these bacteria could have potential for recycling siderurgic waste for steel production.

Transdermal ketamine as an adjuvant for postoperative analgesia after abdominal gynecological surgery using lidocaine epidural blockade.

UNLABELLED: We examined the postoperative analgesia of a controlled delivery ketamine transdermal patch after minor abdominal gynecological surgery using lidocaine epidural blockade. Fifty-two patients were randomized to one of two groups. Epidural anesthesia was performed with 25 mL 2% plain lidocaine. At the end of the surgical procedure, a controlled delivery transdermal patch containing either ketamine (25 mg/24 h) (Ketamine group) or placebo (Placebo group) was applied. Pain and adverse effects were assessed hourly postoperatively for 24 h. IM dipyrone was available at patient request. The two groups were demographically similar. The time to first rescue analgesic was longer in the Ketamine group (230+/-112 min) compared with the Placebo group (94+/-54 min); (P<0.00001). There were more dipyrone dose injections in 24 h in the Placebo group compared with the Ketamine group (P<0.0001). The incidence of adverse effects was similar between groups. We conclude that the transdermal-controlled delivery of ketamine prolonged the duration of analgesia after minor gynecological procedures. IMPLICATIONS: Transdermal delivery of ketamine was an useful adjuvant to postoperative analgesia after epidural lidocaine blockade in the population studied.

Transdermal nitroglycerine enhances spinal neostigmine postoperative analgesia following gynecological surgery.

BACKGROUND: Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia. METHODS: Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 microgram). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05). CONCLUSION: Although neither intrathecal 5 microgram neostigmine alone nor transdermal nitroglycerine alone (5 mg/day) delayed the time to administration of first rescue analgesics, the combination of both provided an average of 14 h of effective postoperative analgesia after vaginoplasty, suggesting that transdermal nitroglycerin and the central cholinergic agent neostigmine may enhance each other's antinociceptive effects at the dose studied.

Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management.

BACKGROUND: Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy. METHODS: After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4. RESULTS: The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not. CONCLUSIONS: Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.

Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia.

BACKGROUND: Intrathecal neostigmine produces analgesia in volunteers and patients. However, the use of epidural neostigmine has not been investigated. The purpose of the current study was to define the analgesic effectiveness of epidural neostigmine coadministered with lidocaine and side effects in patients after minor orthopedic procedures. METHODS: After Institutional Review Board approval and informed consent, 48 patients (n = 12) undergoing knee surgery were randomly allocated to one of four groups and studied in a prospective way. After 0.05-0.1 mg/kg intravenous midazolam premedication, patients were randomized to receive 20 mg intrathecal bupivacaine plus epidural lidocaine (85 mg) with saline (control group); 1 microg/kg epidural neostigmine (1 microg group); 2 microg/kg epidural neostigmine (2 microg group); or 4 microg/kg epidural neostigmine (4 microg group). The concept of the visual analog scale, which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. Postoperatively, pain was assessed using the visual analog scale, and intramuscular 75 mg diclofenac was available at patient request. RESULTS: Groups were demographically the same and did not differ in intraoperative characteristics (blood pressure, heart rate, ephedrine consumption, oxyhemoglobin saturation, sensory loss before start of surgery, or duration of sensory motor block). The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). The time (min +/- SD) to first rescue analgesic was as follows: control group: 205+/-48; 1-microg group: 529+/-314; 2-microg group: 504+/-284; 4-microg group: 547+/-263 (P < 0.05). The analgesic consumption (number of intramuscular diclofenac injections [mean, 25th-75th percentile]) in 24 h was as follows: control group: 3 [3 or 4]; 1-microg group: 1 [1 or 2]; 2-microg group: 2 [1 or 2]; 4-microg group: 2 [1-3] (P < 0.05). The 24-h-pain visual analog scale score (cm +/- SD) that represents the overall impression for the last 24 h was as follows: control group: 5+/-1.6; 1-microg group: 1.6+/-1.8; 2-microg group: 1.4+/-1.6; 4-microg group: 2.2+/-1.9 (P < 0.005). The incidence of adverse effects was similar among groups (P > 0.05). CONCLUSION: Epidural neostigmine (1, 2, or 4 microg/kg) in lidocaine produced a dose-independent analgesic effect (approximately 8 h) compared to the control group (approximately 3.5 h), and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.

Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia following orthopedic surgery.

BACKGROUND: Sufentanil is a potent but short-acting spinal analgesic used to manage perioperative pain. This study evaluated the influence of transdermal nitroglycerine on the analgesic action of spinal sufentanil in patients undergoing orthopedic surgery. METHODS: Fifty-six patients were randomized to one of four groups. Patients were premedicated with 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline or 10 microg sufentanil). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control group received spinal saline and transdermal placebo. The sufentanil group received spinal sufentanil and transdermal placebo. The nitroglycerin group received spinal saline and transdermal nitroglycerine patch. Finally, the sufentanil-nitroglycerin group received spinal sufentanil and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: The time to first rescue analgesic medication was longer for the sufentanil-nitroglycerin group (785+/-483 min) compared with the other groups (P<0.005). The time to first rescue analgesics was also longer for the sufentanil group compared with the control group (P<0.05). The sufentanil-nitroglycerin group group required less rescue analgesics in 24 h compared with the other groups (P<0.02) and had lesser 24-h pain visual analog scale scores compared with the control group (P<0.005), although these scores were similar to the sufentanil and nitroglycerin groups (P>0.05). The incidence of perioperative adverse effects was similar among groups (P>0.05). CONCLUSIONS: Transdermal nitroglycerine alone (5 mg/day), a nitric oxide generator, did not result in postoperative analgesia itself, but it prolonged the analgesic effect of spinal sufentanil (10 microg) and provided 13 h of effective postoperative analgesia after knee surgery.

Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy.

STUDY OBJECTIVE: To examine analgesia and adverse effects of combination epidural pain therapy consisting of administration of morphine with either low dose of ketamine, neostigmine, or midazolam in terminal cancer pain patients. DESIGN: Randomized double-blind study. SETTING: Teaching hospital. PATIENTS: 48 terminal cancer patients suffering from chronic pain. INTERVENTIONS: Patients were randomized to one of four groups (n = 12). The concept of visual analog scale (VAS), which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. All patients were taking oral amitriptyline 50 mg at bedtime. Pain was initially treated with epidural morphine 2 mg twice daily (12-hr intervals) to maintain the VAS below 4/10. Afterwards, VAS scores > or = 4/10 at any time were treated by adding the epidural study drug (2 ml), which was administered each morning, just after the 2-mg epidural morphine administration. The control group (CG) received 2 mg of epidural morphine (2 ml). The ketamine group (KG) received 0.2 mg/kg epidural ketamine (2 ml). The neostigmine group (NG) received 100 micrograms epidural neostigmine (2 ml). The midazolam group (MG) received 500 micrograms epidural midazolam (2 ml). Patients received the study drugs on a daily basis. MEASUREMENTS AND MAIN RESULTS: Duration of effective analgesia was measured as time from the study drug administration to the first patient's VAS score > or = 4/10 recorded in days. The groups were demographically the same. The VAS pain scores prior to the treatment were also similar among groups. Only the patients in the KG demonstrated lower VAS scores compared to the MG (p = 0.018). Time since the epidural study drug administration until patient complaint of pain VAS > or = 4/10 was higher for both the KG and NG compared to the CG (KG > CG, p = 0.049; NG > CG; p = 0.0163). Only the KG used less epidural morphine compared to the CG during the period of study (25 days) (p = 0.003). CONCLUSION: The association of either low-dose epidural ketamine or neostigmine (but not midazolam) to epidural morphine increased the duration of analgesia in the population studied (gt;20 days) compared to the CG and MG (8 to 10 days) when administered in the early stages of terminal cancer pain therapy, without increasing the incidence of adverse effects.

Combined intrathecal fentanyl and neostigmine: therapy for postoperative abdominal hysterectomy pain relief.

STUDY OBJECTIVE: To evaluate the analgesic action of spinal neostigmine as part of a multimodal analgesic therapy approach including spinal neostigmine and spinal fentanyl for postoperative pain relief DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 50 ASA physical status I and II patients undergoing abdominal hysterectomy. INTERVENTIONS: Patients were assigned to one of five groups (n = 10) to receive 15 mg bupivacaine plus 1 ml of the test drug intrathecally. The control group (CG) received saline as the test drug, the fentanyl group (FG) received 25 microg fentanyl; the neostigmine group (NG) received 25 microg neostigmine; the fentanyl-neostigmine 10 microg group (FNG10) was given 10 microg fentanyl plus 10 microg neostigmine; and the fentanyl-neostigmine 25 microg group (FNG25) received 25 microg fentanyl plus 25 microg neostigmine. Pain and nausea were evaluated using a 10-cm visual analog scale (VAS). MAIN RESULTS: The analgesic consumption, in 24 hours was greatest in CG, next highest in NG, FG, and FNG10 where consumption was the same in the three groups; and least in FNG25 (p < 0.05). The time to first rescue analgesic medication was greatest for FNG25 compared with the other groups (>5 hours compared with 2 to 3 hours; p < 0.05). VAS showed no statistically significant differences for pain impression, intraoperative and postoperative nausea, or occurrence of vomiting (p > 0.05). CONCLUSION: The combination of 25 microg neostigmine with 25 microg fentanyl given intrathecally with 15 mg of hyperbaric bupivacaine delayed postoperative pain and lowered the number of rescue analgesics. Because the better quality of analgesia was obtained with an increased (although not statistically significant difference) incidence of untoward side effects, larger samples should be studied before its routine use is recommended.