Nursing activities directed at maintaining patient comfort incorporates time and energy. Nurses and researchers continue to search for adequate methods and information to quantify pain. The common mode of therapy is the administration of narcotics, which do not consistently relieve the pain described by traumatically injured patients. Discovery of endogenous opiates, such as β-endorphins, provided the potential for acquiring additional physiologic information regarding neuro-endocrine activities associated with pain. Consistent findings of concentrated β-endorphins in areas of the central nervous system previously identified as pain pathways prompted clinical researchers to determine β-endorphin levels in patients experiencing pain. The purposes of this investigation were to study β-endorphin levels in burn injured patients by describing: (1) the pattern of β-endorphin levels in burn injured patients during the first two weeks following injury, (2) the relationship between β-endorphin levels and the severity of the burn injury, (3) the relationship between analgesia taken by patients and the severity of the burn, and (4) the relationship between β-endorphin levels and the amount of analgesia given to the burn patient. Plasma samples for β-endorphin levels were obtained from 28 burned patients over a two-week interval. New England Nuclear ¹²⁵I β-Endorphin Kits were used to assay the plasma samples. In addition, information was tabulated from the patient's chart to complete the Burn Severity Index. Narcotic analgesia taken 24 hours before obtaining the blood sample were summarized and categorized according to the Equianalgesia Table. Descriptive and correlational statistics showed no significant relationships between β-endorphins over time, β-endorphins with burn severity, β-endorphins with the analgesia equivalency score, or burn severity with the analgesia equivalency scores. β-endorphin levels were elevated above normal in all 28 patients. Five patients displayed the anticipated declining pattern over the two-week interval post burn. Many erratic peaks and troughs in β-endorphin levels were observed with some peaks associated with clinical events. The findings of elevated β-endorphin levels have implications for nursing practice and provide stimulus for continued nursing research.

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Modeling is a valuable tool in drug development, to support decision making, improving study design, and aid in regulatory approval and labeling. This thesis describes the development of pharmacometric models for drugs used in anesthesia and analgesia. Models describing the effects on anesthetic depth, measured by the bispectral index (BIS), for a commonly used anesthetic, propofol, and for a novel anesthetic, AZD3043, were developed. The propofol model consisted of two effect-site compartments, and could describe the effects of propofol when the rate of infusion is changed during treatment. AZD3043 had a high clearance and a low volume of distribution, leading to a short half-life. The distribution to the effect site was fast, and together with the short plasma half-life leading to a fast onset and offset of effects. It was also shown that BIS after AZD3043 treatment is related to the probability of unconsciousness similar to propofol. In analgesia studies dropout due to lack of efficacy is common. This dropout is not at random and needs to be taken into consideration in order to avoid bias. A model was developed describing the PK, pain intensity and dropout hazard for placebo, naproxen and a novel analgesic compound, naproxcinod, after removal of a wisdom tooth. The model provides an opportunity to describe the effects of other doses or formulations. Visual predictive checks created by simultaneous simulations of PI and dropout provided a good way of assessing the goodness of fit when there is informative dropout. The performance of non-linear mixed effects models in the presence of informative dropout, with and without including models that describe such informative dropout was investigated by simulations and re-estimations. When a dropout model was not included there was in general more bias. The bias increased with decreasing number of observations per subject, increasing placebo effect and increasing dropout rate. Bias was relatively unaffected by the number of subjects in the study. The bias had, in general, little effect on simulations of the underlying efficacy score, but a dropout model would still be needed in order to make realistic simulations.

Made available in DSpace on 2014-06-11T19:31:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T21:02:11Z : No. of bitstreams: 1 lorena_sers_dr_botfmvz.pdf: 632999 bytes, checksum: 35174e377fd65ef6483f2f8509b96974 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O uso de analgésicos em animais é justificado moral e cientificamente. Para tal, é necessário que os profissionais saibam reconhecer e tratar a dor de forma adequada em animais. Objetivou-se correlacionar diversos dados demográficos para obter o perfil do médico veterinário brasileiro de grandes e pequenos animais. O questionário da pesquisa foi composto por: dados pessoais, utilização de fármacos analgésicos, analgesia, conduta no alívio da dor, uso de analgésicos em diversos procedimentos de grandes e pequenos animais, avaliação da dor e atualizações. A estatística foi realizada pelo programa SAS for Windows versão 9.1.3 com estatística descritiva com análise de frequência. Para as comparações simples foi utilizado o teste de qui-quadrado (x2). Foram obtidos 1.298 questionários de pequenos animais e 713 de grandes. Mulheres e profissionais graduados havia menos de dez anos conferiram maiores escores de dor que homens e profissionais formados havia mais de dez anos, porém a duração do tratamento não diferiu entre os gêneros. Os opioides mais utilizados para a analgesia foram tramadol (79%) e morfina (50,5%), em cães e gatos, e butorfanol (43,4%) e tramadol (39%) em grandes animais. Os efeitos adversos mais reportados dos opioides em gatos foram depressão respiratória e excitação. Em cães os principais efeitos adversos assinalados foram depressão respiratória e êmese. Para grandes animais, as preocupações com o uso desses fármacos foram: risco de excitação e síndrome cólica equina. Mais de 50% dos veterinários não utilizava opioides em bovinos. Os anti-inflamatórios não esteroidais (AINEs) mais escolhidos para pequenos animais foram meloxicam (81%) e cetoprofeno (70,4%), e flunixin meglumine (83,2%) e cetoprofeno (67,6%) em grandes animais. Os efeitos... / The use of analgesics in animals is morally and scientifically justified. According to that, the professionals should know how to recognize and treat pain in animals. The aim of this study was to correlate the demographic data of the Brazilian veterinarians, with the use of analgesics, the factors that affected the decision on the use of analgesia, attitudes, knowledge and methods of obtaining information on the evaluation and treatment of pain in animals. The questionnaire was composed of demographics, personal data, use of analgesics in general and specific procedures, analgesia, attitudes in the assessment and relief of pain and types of information in the area. The descriptive statistics with frequency analysis was performed using SAS for Windows 9.1.3. Chi-square (x2) for simple comparisons test was used. Questionnaires were obtained from 1298 small and 713 large animal veterinarians. Women and veterinarians graduated for less than ten years attributed higher pain scores than men, and veterinarians graduated for over ten years, but the frequency and duration of analgesic treatment did not differ between gender. The most commonly used opioid for analgesia of small animals were tramadol (79%) and morphine (50.5%) for dogs and cats, and butorphanol (43.4%) and tramadol (39%) for large animals. The most important side effects of opioids in small animals were respiratory depression and excitement, for cats and emesis in dogs and excitement and colic syndrome in 4 horses. NSAIDs of choice for small animals were meloxicam (81%) and ketoprofen (70.4%) and for large animals, flunixin meglumine (83.2%) and ketoprofen (67.6%). Side effects of NSAIDs most frequently reported for all species were gastric changes and nephrotoxicity. The most important limiting factors for the use of NSAIDs and opiods were the side effects for horses and the cost for cattles. The cats received lower pain... (Complete abstract click electronic access below)

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A number of investigators have suggested that the early and late phases of the formalin test are mediated by separate neural systems. Evidence is presented which suggests that in addition to a dissociation between the two phases based on nociceptor stimulation and inflammation, the late phase of the formalin test is also dependent upon plasticity in the central nervous system which occurs during the transient early phase. Selectively blocking neural activity during the early phase with local anesthetics given peripherally, or in the cingulum bundle or fornix, prevents the development of these changes. Locally anesthetizing the cingulum bundle, fornix or medial bulboreticular formation prior to testing in the late phase produces analgesia which exceeds the duration of the anesthetic. It was also demonstrated that a thermal injury to the hindpaw or electrical stimulation of the sciatic nerve prior to neurectomy produces changes in the pattern and severity of self-mutilation following peripheral neurectomy, suggesting that the injury is encoded and maintained in central structures.

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