Dissertations / Theses on the topic 'Intravenous fluid'

Antidiuretic hormone (ADH) is a fundamental regulator of fluid and electrolyte homeostasis. Osmotically unregulated ADH secretion during intravenous fluid therapy has been implicated in the development of iatrogenic hyponatraemia. The case report and 3 prospective studies of this thesis provide evidence for this and examine the relative contributions of salinity versus infusion rate of intravenous fluids to the development of hyponatraemia. Two studies of plasma and urinary electrolytes and osmolality during intravenous rehydration of children with gastroenteritis were performed. The first, an observational study of 52 children receiving 0.45% (N/2) saline documented persistently raised plasma ADH concentrations independent of plasma sodium. In both studies, plasma and urinary biochemistry suggested osmotically unregulated ADH action. When N/2 and NS were compared in a randomised study of 102 children, NS emerged as superior in the prevention and correction of hyponatraemia, independent of infusion rate. In the third study, 124 pre-operative children were randomised to receive N/2 or NS intravenously at 100% or 50% of maintenance rates post-operatively. Plasma ADH concentrations increased in all groups, and the plasma and urinary biochemistry indicated persistent non-osmotic ADH activity in some children for up to 24 hours. Baseline urinary tonicity approximated NS. Comparison of urinary tonicity with the infused fluid largely explained changes observed in plasma sodium. The risk of hyponatraemia was decreased by isotonic saline but not fluid restriction; however plasma sodium concentration decreased in the NS 100% group between 8 and 24 hours, suggesting that a decreased rate should be considered during prolonged intravenous fluid administration. Fourteen (23%; 7NS) of those on 50% maintenance were assessed as dehydrated, with hypernatraemia in 3 receiving NS50%. The chloride load associated with NS in the second and third studies was not associated with the development of acidosis. The studies also showed that 2.5% dextrose resolved and prevented hypoglycaemia in children with gastroenteritis but was inadequate to prevent hypoglycaemia and/or ketosis in 38% of children under 6 years when infused at maintenance rates. Non-osmotically regulated ADH activity in hospitalised children is common, in the face of which, isotonic is superior to hypotonic saline in decreasing the risk of hyponatraemia.

Thesis (Master of Emergency Medical Care)--Cape Peninsula University of Technology, 2018.
Physical injury is a major cause of premature death and disability worldwide (WHO, 2015). Mortality statistics for South Africa indicate that approximately half of all injury-related deaths were intentionally inflicted, often as a result of sharp-force injuries (Donson 2009). Cape Town is reputed to be a violent city (Nicol et al., 2014). Pre-hospital emergency care providers are often the first medical contact for injured patients. Previously, it was understood that high volume crystalloid administration would improve survival and was standardised in the management of shock (Santry & Alam 2010). However, over-administration of crystalloid fluid can cause patient harm by potentially worsening injuries and can be detrimental to a patients survival. Current evidence supports the practice of lower volume crystalloid intravenous fluid administration- permissive hypotension. Little is known about pre-hospital emergency care providers intravenous fluid management practices for penetrating injury. Injury surveillance data for victims of penetrating injury is also scarce with the majority of current data taken from mortality sources. Surveilling pre-hospital cases may yield opportunities for prevention from premature mortality and morbidity. The aim of this study is to undertake surveillance of penetrating injury and related intravenous fluid resuscitation in the pre-hospital emergency care environment. A prospective observational descriptive survey was conducted in the Cape Metropole1. Over three consecutive months, emergency care providers documented parameters related to mechanism of injury, scene vital signs, hospital vital signs, intravenous fluid resuscitation and basic patient demographic information for patients with penetrating injury. A predetermined inclusion and exclusion criteria was used to sample patients.

Thesis (MNutr)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Objectives: The objectives of this study were to determine the nutritional content/ contribution of intravenous (IV) fluid and electrolyte administration on the total feeding prescription of intensive care unit (ICU) patients. Methods: Retrospective review of ICU charts of consecutive patients (>18 years) with APACHE II scores ≥10 and on ≥72 hours nutrition therapy (NT) admitted to a medical/surgical ICU. Total fluid, electrolyte, energy and macronutrient intake from nutritional and non-nutritional sources were reviewed from ICU admission until discharge, discontinuation of NT or death for ≤7 days. Energy and protein delivery were compared to calculated targets of 25.4 – 28.6kCal/kg and 1.3 – 1.5g/kg respectively. Summary statistics, correlation coefficients and appropriate analysis of variance were used to describe and analyse the data. Results: A total of 71 patients (49% male), average age 49.2 ± 17.1, average APACHE II score 21.0 ± 6.1, 68% medical and 32% surgical, were included. Fluid and nutrient intake were reviewed over a mean of 5.7 ± 1.1 days. Mean daily fluid delivery was 3.2 ± 0.6L. IV fluid therapy (IVFT) contributed 32.0 ± 12.0% to total fluid delivery (TFD), whereas IV drug administration, including fluids used for reconstitution and dilution purposes, contributed 20.7 ± 8.1% to TFD. Balanced electrolyte solutions (BES) were the crystalloid of choice, prescribed in 91.5% of patients with a mean daily volume (MDV) of 0.5 ± 0.4L. Hypertonic low molecular weight (LMW) 130/0.4kD hydroxyethyl starch (HES) was the colloid of choice, prescribed in 78.9% of patients with a MDV of 0.2 ± 0.1L. Potassium salts were the most frequently prescribed IV electrolyte supplement (IVES), prescribed in 91% of patients (±20 – 60mmol per administration). NT was initiated within 14.5 ± 14.1 hours. The majority (80%) received enteral nutrition (EN). The mean daily energy delivered was 1613 ± 380kCal (25.1kCal/kg), meeting 93.6 ± 17.7% of mean target range (MTR). Mean daily protein delivery (PD) was 72 ± 22g (1.1g/kg), meeting 82.8 ± 19.9% of MTR. Non-nutritional energy sources (NNES), mostly derived from carbohydrate-containing IV fluids, contributed 10.1 ± 7.5% to total energy delivered (156kCal/d). Mean cumulative energy and protein balance was -674.0 ± 1866.1kCal and -86.0 ± 106.9g respectively. The majority (73%) received >90% of the minimum energy target but only 49% >90% of minimum protein target; 59% of those with energy intake 90-110% of target had adequate protein intake. A significant negative correlation was found between cumulative energy/protein balance and the time to initiation of NT (energy: r=-0.28, p=0.02; protein: r=-0.32, p=0.01). Conclusion: In this ICU BES are the crystalloid of choice and hypertonic LMW 130/0.4kD HES the colloid of choice for IVFT. Potassium salts are the most frequently prescribed IVES. NNES added significantly to energy delivery and should be included in the calculation of feeding prescriptions to avoid the harmful effects of overfeeding. Early initiation of EN with conventional products which are energy rich is insufficient to achieve adequate PD. EN formulae with a more favorable nitrogen to non-protein energy ratio could help to optimise PD during the first week of ICU care.
AFRIKAANSE OPSOMMING: Doelwitte: Die doelwit van hierdie studie was om die voedingswaarde/ bydrae van intraveneuse (IV) vog en elektroliet toediening tot die totale voedings voorskrif van pasiënte in ‘n intensiewe sorg eenheid (ISE) te bepaal. Metodes: Retrospektiewe bestudering van die ISE kaarte van agtereenvolgende pasiënte (>18 jaar) opgeneem in ‘n mediese/chirurgie ISE en met APACHE II tellings ≥10 en ≥72 ure voedingsterapie (VT). Totale vog, elektroliet, energie en makronutriënt inname vanaf voedingsverwante en nie-voedingsverwante bronne is vanaf ISE opname tot en met ontslag, staking van VT of sterfte, vir ≤7 dae hersien. Energie en proteiën inname is vergelyk met berekende doelwitte van 25.4 – 28.6kKal/kg en 1.3 – 1.5g/kg onderskeidelik. Beskrywende statisitiek, korrelasie koeffisiënte en toepaslike analises van variansie is gebruik vir data analise. Resultate: 71 pasiënte (49% mans), gemiddelde ouderdom 49.2 ± 17.1, gemiddelde APACHE II telling 21.0 ± 6.1, 68% medies en 32% chirurgie, is ingesluit. Vog en voedingstof inname is hersien oor ‘n gemiddelde tydperk van 5.7 ± 1.1 dae. Gemiddelde vog inname was 3.2 ± 0.6L/dag. IV vog terapie (IVVT) het 32.0 ± 12.0% bygedra tot totale vog inname (TVI). IV medikasie toediening, insluitende die herkonstruksie en verwatering van medikasie, het 20.7 ± 8.1% bygedra tot TVI. Die mees voorgeskrewe kristalloiëd en kolloiëd vir IVVT was gebalanseerde elektroliet oplossings (GEO), voorgeskryf in 91.5% van pasiënte (gemiddeld 0.5 ± 0.4L/dag), en hipertoniese lae molekulêre gewig (LMG) 130/0.4kD hidroksie-etiel stysel (HES), voorgeskryf in 78.9% van pasiënte (gemiddeld 0.2 ± 0.1L/dag), onderskeidelik. Die mees voorgeskrewe IV elektroliet supplement was kalium soute, voorgeskryf in 91% van pasiënte (±20 – 60 mmol per toediening). VT is binne 14.5 ± 14.1 ure geinisieër. Die meerderheid (80%) het enterale voeding (EV) ontvang. Die gemiddelde daaglikse energie inname van 1613 ± 380kCal (25.1kKal/kg) het 93.6 ± 17.7% van die gemiddelde doelwit rykwydte (GDR) bereik. Die gemiddelde daaglikse proteiën inname van 72 ± 22g (1.1g/kg) het 82.8 ± 19.9% van die GDR bereik. Nie voedings-verwante energie bronne (NVEB), meestal vanaf koolhidraat-bevattende IV vloeistowwe, het 10.1 ± 7.5% tot totale energie inname (TEI) bygedra (156kKal/d). Die gemiddelde kumulatiewe energie en proteiën balans was -674.0 ± 1866.1kKal en -86.0 ± 106.9g onderskeidelik. Die meerderheid (73%) het >90% van die minimum energie doelwit (ED) bereik. Slegs 49% het >90% van die minimum proteiën doelwit (PD) bereik. Opsomming: Die kristalloiëd en kolloiëd van keuse vir IVT is GEO en hipertoniese LMG 130/0.4kD HES onderskeidelik. Kalium soute word mees algemeen voorgeskryf. NVEB dra beduidend by tot TEI en moet inaggeneem word tydens die berekening van voedingsvoorskrifte ten einde oorvoeding te voorkom. Vroeë inisiëring van EV met konvensionele energie-ryke EV produkte is onvoldoende om genoegsame proteiën inname te verseker. EV produkte met ‘n gunstiger stikstof tot nie-proteiën energie verhouding sal help om proteiën inname gedurende die eerste week van intensiewe sorg te optimaliseer.Slegs 59% van pasiënte met genoegsame energie inname (90-110% van ED) het hul minimum PD bereik. Daar was ‘n beduidende negatiewe korrelasie tussen kumulatiewe energie/proteiën balans en die tyd tot inisiëring van VT (energie: r=-0.28, p=0.02; proteiën: r=-0.32, p= 0.01).

Background Peri-operative physicians increasingly acknowledge that fluid management influences patient outcome. Studies have attempted to understand the changes in practice following recently published evidence, although none have included significant contributions from South Africa. Methods An observational cohort study using an interactive online survey was conducted. Five underlying questions where highlighted during data analysis and these data were summarized into simplified categories for better comparison. Results Three hundred questionnaires where completed. During resuscitation of an unstable trauma patient, 233/300 (78%) use crystalloids, although 107/300 (36%) prefer blood products if available. Synthetic colloids for trauma patients unresponsive to initial fluid (normal haemoglobin) would be chosen first by 179/300 (60%), and 12/28 (46%) of non-anaesthesia physicians prefer blood products. Of interest, 10/300 (3%) would use either albumin or hypertonic saline when resuscitating a non-responding trauma patient. Concerning was 14/300 (5%) of respondents who would use fluid other than blood products for trauma patients with low haemoglobin. A relatively large proportion 47/300 (16%) would use synthetic colloids to resuscitate haemodynamically unstable septic patients. Conclusion The results presented are largely from anaesthesia practitioners and practice follows international trends. However, synthetic colloids are used in septic patients where evidence suggests otherwise. A lack of access to blood products probably influences practice. Findings suggest the need for continued attempts to translate research into clinical practice.

A quasi-experimental research design was used to determine the relationship between the flow rate and the delivered temperature of prewarmed crystalloid intravenous solutions when using the Thermal Jacket™, an insulation device designed for intravenous fluid bags, as compared to a conventional blood warming apparatus. One control and three experimental groups were used. Fluids in Group 1 (control group), Group 2, and Group 4 were prewarmed in a microwave oven to 41.45 ± 1.05 ° C. Fluids in Group 3 were left near ambient room temperature and measured at 22.05 ± 0.45 ° C. Fluids in the control group were infused through a standard intravenous pump tubing, 270 em in length, using no temperature maintenance device. Fluids in Group 2 and Group 3 were delivered through a standard intravenous pump tubing connected to a blood warming coil which was immersed in a water bath blood warmer. The distance from the exit point of the blood warmer to the distal end of the infusion line measured 174 em. Fluids in Group 4 were placed in a Thermal Jacket™ and delivered through standard intravenous pump tubing. After a baseline measurement, temperatures were recorded for all groups at two sites at 10 minute intervals over a 60 minute period. One site was the lower portion of the IV solution bag, and the other site was a point 2 em from the distal end of the infusion set. Temperatures were measured at flow rates of 100, 250, 500, 750, and 1,000 ml/hr for each group. Analysis of variance showed a highly significant group effect on the delivered temperature. A Bonferroni multiple comparisons test indicated no statistically significant difference between the delivered temperatures of Group 3 (room temperature fluid + blood warmer) and Group 4 (prewarmed fluid + Thermal Jacket™). Group 2 (prewarmed fluid + blood warmer) showed a significantly higher delivered temperature (p < .05) than the other groups, and the control group (prewarmed + no temperature maintenance device) showed a significantly lower delivered temperature (12. < .05). Analysis of variance also showed a highly significant flow rate effect on delivered temperature. A Bonferroni multiple comparisons indicated a significant difference (12. < .05) between the flow rates of 100, 250, 500, and 750 ml/hr, with the higher flow rates resulting in higher delivered temperatures. There was no significant difference noted between the delivered temperatures at 750 and 1,000 ml/hr. The Thermal Jacket™, used with prewarmed intravenous fluids, was as effective as the conventional method of delivering warmed fluids. Also, within the range of flow rates studied, faster flow rates tended to yield a higher delivered temperature.

Systemic hydration, plasma electrolytes, ingesta and fecal hydration and gastrointestinal passage of cobalt (after CoEDTA administration via nasogastric tube) in horses fed large grain meals or treated with enteral fluid therapy, IV fluid therapy and enteral laxatives were investigated. In the first study, 0.9% NaCl (10 L/h/8h) was administered slowly via a small-bore nasogastric tube or as 10 L boluses via a large-bore nasogastric tube to four normal horses. In the other studies, horses with a right dorsal colon fistula were used. To create the right dorsal colon fistula, a cannula with 5 cm internal diameter was implanted 2 to 6 weeks after a right dorsal colopexy had been created. Six horses with the right dorsal colostomy were alternately used to test three feeding regimes for 48 h: 1- hay free choice; 2- hay free choice plus 4.5 kg of sweet feed twice daily after a period of 5 days of adaptation; 3- sudden change from hay to hay plus sweet feed. Seven horses with the right dorsal colostomy were alternately used to test 6 experimental conditions while fasted for 24 h: 1- control (no treatment), 2- enteral MgSO4 (1 g/kg), 3- enteral Na2SO4 (1 g/kg), 4- IV lactated Ringer's solution (5 L/h/12 h), 5- enteral water (5 L/h/12 h), 6- enteral electrolyte solution (5 L/h/12 h). In the last study, four horses with the right dorsal colostomy were alternately treated with enteral electrolyte solution (10 L/h/6h) and enteral MgSO4 (1 g/kg) plus IV fluid therapy (10 L/h/6h). Despite the administration regimen, enteral administration of 0.9% NaCl produced diarrhea, hypernatremia and hyperchloremia. Colostomy allowed serial collection of large ingesta samples. Grain ingestion did not change PCV or plasma protein, but affected plasma electrolytes and produced dehydration of ingesta and formation of frothy ingesta. Fasting delayed gastrointestinal transit. Enteral fluid therapy was the most effective treatment in promoting ingesta hydration. Enteral water, MgSO4, Na2SO4, IV fluid therapy and enteral MgSO4 plus IV fluid therapy were either ineffective in promoting ingesta hydration or produced marked plasma electrolyte imbalance. These findings support the use of enteral fluid therapy in horses with gastrointestinal impaction.
Ph. D.

Dissertação de Mestrado Integrado em Medicina Veterinária
A fluidoterapia é uma prática frequente em clínica de equinos, essencialmente em patologias capazes de induzir uma alteração hemodinâmica como em casos de choque endotoxémico. Em clínica de equinos as vias mais utilizadas são a intravenosa e a oral. A via intravenosa é a via de eleição quando é pretendido um efeito rápido, por haver deposição de fluido directamente na corrente sanguínea. É, no entanto, a mais dispendiosa. Pode também recorrer-se à via oral, menos invasiva e útil em impactações ou deslocamentos de cólon. A presença de refluxo enterogástrico ou diminuição da motilidade gastrointestinal são contra-indicação absoluta para esta via. O objectivo do presente estudo realizado neste trabalho é comparar os efeitos sistémicos da fluidoterapia oral, IV e rectal, para determinar se esta ultima é ou não uma alternativa viável à via oral. Um grupo de seis cavalos recebeu três sessões de fluidoterapia por vias de administração diferentes, com intervalo mínimo de cinco dias entre elas. Os parâmetros avaliados foram o hematócrito, a concentração de proteínas plasmáticas e a frequência cardíaca, medidos com intervalos de 15 minutos. Foi feita também uma avaliação subjectiva da quantidade de urina produzida e da frequência de defecação e consistência das fezes. A solução utilizada foi o NaCl 0,9 % para as três vias de administração. Nas vias oral e rectal foram administrados 4 litros com intervalo de 20 minutos durante os primeiros 80 minutos e 4 litros com intervalo de 30 minutos até perfazer os 40 litros. Na via intravenosa foi usada uma taxa de administração contínua e 5 litros/hora. Nas três vias utilizadas os valores de hematócrito diminuíram ao longo da experiência. Na via oral e na rectal as alterações foram semelhantes, enquanto que na via endovenosa a descida foi mais rápida e profunda. Não se verificaram alterações estatisticamente significativas na concentração de proteínas plasmáticas. A via rectal revelou-se uma via de hidratação eficaz e uma alternativa viável à via de administração oral.
ABSTRACT - Analogy between different methods of administrating fluids in horses: Intravenous, Enteric and Rectal. - Fluid Therapy is a regular practice in horse clinic, essentially regarding pathologies capable of inducing a hemodynamic change, as seen in cases of endotoxic shock. In horse clinic, the most recurring methods of fluid administration are the intravenous and the oral. The intravenous method is the favoured one when a fast effect is pretended, due to the direct deposition of fluid in the blood flow. However, it is the most expensive. The oral method may also be utilized, less invasive and useful for impactions or colon displacement. The presence of enterogastric reflux or the decrease of gastrointestinal motility is an absolute contraindication for the use of this method. The goal of the analysis carried out in this work is to compare the systemic effects of the oral, intravenous and rectal fluid therapy, in order to determine if the latter is a consistent alternative to the oral method. A group of six horses has received three sessions of fluid therapy using different methods, with a minimum time gap of five days in between. The evaluated parameters were the haematocrit, the concentration of plasma proteins and the heart-rate, measured every 15 minutes. A subjective evaluation has also been done of the amount of produced urine, the frequency of defecation and the consistency of the faeces. The solution applied was the NaCl 0,9 % for the three methods of administration. Regarding the oral and rectal methods, 4 litres were given with 20-minute intervals during the first 80 minutes and 4 litres with the 30-minute interval until completing the 40 litres. For the intravenous method, a continuous rate of administration was used and 5 litre per hour. In the three methods, the haematocrit values have decreased throughout the experience. In the oral and rectal method, the changes were similar, whereas the decrease was faster and deeper in the intravenous method. There have not been any statistically significant changes on the concentration of plasma proteins. The rectal method has been proved to be an effective hydration method and a viable alternative to the oral administration.

Dissertação de Mestrado Integrado em Medicina Veterinária
O Síndrome de Abdómen Agudo é uma patologia muito frequentemente encontrada na prática clínica de equinos. A hidratação dos cavalos com dor abdominal aguda é extremamente importante. Por este motivo, a abordagem terapêutica médica destes animais inclui quase invariavelmente a administração de fluidos. O médico veterinário pode recorrer à fluidoterapia entérica e à fluidoterapia endovenosa para o tratamento destes animais, podendo utilizá-las isoladamente ou em conjunto. A elaboração de um plano de fluidoterapia, seja entérica e/ou endovenosa, deve ser baseada na alteração clínica apresentada pelo animal. Nos casos de maior gravidade, nos quais os pacientes se apresentam com um grau de desidratação moderado a grave, a administração de fluidos por via endovenosa é imprescindível. Nestes casos, e também de modo a diminuir os custos económicos associados à fluidoterapia endovenosa, a fluidoterapia entérica pode ser considerada como um complemento sempre que não se verifique a presença de refluxo enterogástrico. A presença de refluxo enterogástrico é indicadora de disfunção gastrointestinal grave associada com o comprometimento das funções de secreção e absorção do intestino ou com alterações de trânsito intestinal, e constitui uma contra-indicação absoluta para a administração de fluidos por via entérica. A fluidoterapia entérica deve ser reservada para os casos de SAA associados com alterações hidroelectrolíticas ligeiras. Esta via de administração de fluidos representa um método rápido e económico para promover a hidratação dos conteúdos intestinais. Recentemente têm vindo a surgir cada vez mais evidências da eficácia da administração de fluidos por via entérica em casos de obstruções simples de intestino grosso (impactações e deslocamentos de cólon maior). De facto, nos casos de impactações intestinais não complicadas, faz mais sentido promover a hidratação da ingesta através de fluidoterapia entérica, provocando assim efeitos mínimos ao nível da circulação sistémica. Apesar de não se poderem substituir uma à outra, estas duas formas de administração de fluidos são fundamentais na abordagem médica aos casos de SAA em equinos pela sua complementaridade.
ABSTRACT - Enteral Fluid Therapy versus Intravenous Fluid Therapy in Equine Acute Abdomen - The acute abdomen is a very common feature in equine practice. The hydration of the horse with acute abdominal pain is extremely important, thus the treatment of these animals includes very often fluids administration. The equine practitioner can use enteral fluid therapy or intravenous fluid therapy alone or together for acute abdominal pain treatment. The fluid plan elaboration, whether enteral and/or intravenous, should be based on the animal clinical condition. In more serious cases the intravenous fluids administration is essential. Also in these cases, to reduce the costs associated to intravenous fluid therapy, enteral fluids can be used as a complement when there is no gastric reflux, which indicates a serious gastrointestinal dysfunction associated with motility disorders or impaired intestinal absorption and secretion mechanisms. So, gastric reflux is an absolute contraindication for the use of enteral fluids. The enteral fluid therapy should be reserved for acute abdomen cases associated with mild hydroelectrolyte disorders. The administration of enteral fluids represents a quick and economical method to promote the hydration of intestinal contents. There are some recent scientific reports that support the efficacy of enteral fluid therapy in mild cases of large intestinal obstruction (impactions and displacements). In fact, in uncomplicated impactions, it makes more physiological sense to promote direct ingesta hydration while having minimal effects on the systemic circulation. Although one can not replace the other, these fluid administration routes are essential and complementar in the medical management of equine acute abdomen cases.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
The role of enzyme‐assisted subcutaneous fluid administration (EASFA) in treating mild to moderate dehydration in pediatrics, geriatrics, and palliative care has been studied in developed countries. However, it has historically been underutilized due to widely available health care and alternative treatments, namely peripheral intravenous (IV) fluid administration. Fluid infusions in the subcutaneous tissue have a low risk of infection, are easy to administer, and have wide potential use. The use of EASFA in low resource settings to treat those with difficult IV access or where skilled healthcare workers are not as readily available could prove to be a live saving measure in many situations, including the care of patients in remote areas of the world, mass casualty events, or other disasters. Our objective was to determine if EASFA is a valid and appropriate technique to utilize in pediatric and elderly patients, and evaluate if it could be a safe and efficient way to provide fluid resuscitation in low resource settings. For this systematic review MEDLINE and Cochrane Library were searched from January 1950 to December 2015 to recover all available literature relevant to this topic. Studies that met the inclusion criteria were analyzed using Cohen’s D. This was calculated using the mean difference between intervention and control divided by the pooled standard deviation. For dichotomous outcome of the placement success rate the odds ratios were calculated with 95% confidence intervals. In reviewing 7 articles using Cohen’s D to compare mean differences to determine effect size, we found that catheter placement success rates and infusion rates were similar between EASFA and peripheral intravenous fluid administration. Additionally, it was found that the odds of correct initial needle placement was 7.19 times higher in EASFA versus intravenous administration. EASFA is a comparable alternative to intravenous fluid administration when delivering fluids to pediatric and elderly patients with mild to moderate dehydration. While infusion rates and total volume of fluids administered were similar, the high rate of success with placement of the subcutaneous catheter proves it to be more useful in some situations. Venous cannulation is difficult, even for a trained healthcare provider, and the ease of placement of subcutaneous catheters makes training lay people to administer subcutaneous fluids a possibility. Additionally, this type of fluid administration may lead to less psychological trauma to a child from multiple needle sticks, while still achieving a similar outcome of effective volume replacement. Based on the results of this study, further research is needed to evaluate the effectiveness of utilizing EASFA in low resource settings.

O presente trabalho visa desenvolver métodos que permitam determinar as concentrações de tetraciclina, por Cromatografia Líquida de Alta Eficiência, no plasma e líquido sinovial, além de analisar as concentrações correspondentes em leite de gado leiteiro em lactação submetidos aos tratamentos intravenoso e intravenoso regional. Desta forma, objetivando determinar a depuração da tetracic1ina no organismo dos animais tratados, a concentração do fármaco no sítio de ação e a quantidade residual em leite, as amostras biológicas foram colhidas e quantificadas em diferentes tempos pré e pós-administração do fármaco. Os métodos analíticos validados apresentaram linearidade, limite de detecção, quantificação, exatidão, precisão e recuperação adequados à quantificação do antibiótico nas matrizes biológicas estudadas. As amostras de leite de animais tratados com o medicamento por via intravenosa regional, não apresentaram resíduos após 120h da administração do fármaco. O mesmo ocorreu plasma e líquido sinovial após 48 h. Através da administração via intravenosa do medicamento foram observados resíduos no leite em todos os tempos avaliados, ao passo que no plasma e líquido sinovial, a presença do princípio ativo não foi detectada após 72 horas pós-tratamento.
The purpose of the present work is to develop methods which allow the determination of tetracycline by High Pressure Liquid Chromatography in serum, synovial fluid, as well as analyze the corresponding milk concentrations in milk cows subjected to intravenous and regional intravenous treatment. Therefore, aiming to determine the clearance of tetracycline in the body of the treated animals, the concentration of the active principle in the action site and the residual quantity in milk, biological matrices were collected at different times. The validated analytical methods depicted suitable linearity, detection and quantification limits, accuracy, precision and recovery, allowing the quantification of the antibiotic in the studied biological matrices. In relation to the milk samples from animals treated with the drug by regional intravenous via, they did not present residues of tetracycline after 120 h post-administration. The values were also null for both serum and synovial fluid after 48 h. Through regional intravenous drug administration, milk residues were observed in all the evaluated times whereas for serum and synovial fluid, the presence of the active principle was not detected after 72h post-treatment.

The intravenous administration of fluids in shock is life saving. However, there is increasing controversy as to the rationale for the normalisation of blood pressure in the treatment of shock with either colloids or crystalloids. Increasing the blood pressure by either the administration of colloids or crystalloids may also impair the formation of new blood clots and also dislodge existing ones and thus contribute to ongoing haemorrhage. The main aim of this thesis was to investigate the intrinsic and volumetric effect that these different intravenous resuscitation fluids have on the haemostatic process and bleeding. A variety of studies including in vitro mechanistic investigations, electron microscopy, randomised trials, randomised and double blinded trials were carried out. These were supported by epidemiological and systematic literature reviews to clarify the controversy.

Dentre as afecções que acometem as articulações dos equinos, a artrite séptica e a mais grave observada. A técnica da perfusão regional e um método comprovadamente eficiente para o tratamento de equinos acometidos por infecções sinoviais. O dimetilsulfóxido (DMSO) é um líquido orgânico, que possui a capacidade de penetrar, com extrema facilidade, em órgãos, tecidos e membranas celulares e intracelulares. Neste estudo, objetivou-se avaliar a concentração intra-articular da gentamicina administrada por perfusão regional intravenosa (PRI), associada ou não ao DMSO, bem como avaliar a influência do volume total perfundido o período de tempo onde a concentração inibitória mínima (CIM) foi mais eficiente e se a associação com o DMSO aumentou a CIM no líquido sinovial. Os animais foram distribuídos em quatro grupos experimentais, cada grupo recebeu gentamicina 6,6 mg/kg por PRI, o volume a ser administrado, após o cálculo da quantidade de gentamicina acrescida ou não de DMSO, era completado com solução de ringer com lactato estéril até o volume de 60mL nos grupos G60 e GD60, e até 250mL para os grupos G250 e GD250. As colheitas de líquido sinovial foram realizadas antes do início do experimento (T0), imediatamente depois da retirada do torniquete (T1) e após 4 (T2), 8 (T3), 12 (T4), 16 (T5) e 24 (T6) horas. O método para doseamento das concentrações de gentamicina empregado foi o de difusão em ágar. Destacamos que as concentrações de gentamicina no líquido sinovial na dose de 6.6.mg/Kg podem ser consideradas como adequadas, num período de até 24 horas após a administração. Nossos resultados apontam que o volume de 60 mL, pode ser considerado como o volume ideal de perfusão, bem como a associação do DMSO aumentou as concentrações de gentamicina (µg/mL) na articulação dos equinos e possivelmente reduziu a formação de edemas e aumentos de volume locais.
Among the diseases that affect the joints of horses, septic arthritis is the most serious observed. The regional perfusion technique is a well proven method for the treatment of horses affected by synovial infections. Dimethylsulfoxide (DMSO) is an organic liquid that has the ability to penetrate, with extreme ease on organs, tissues and cellular and intracellular membranes. This study aimed to evaluate the intra-articular concentration of gentamicin administered by intravenous regional perfusion (PRI), associated or not with DMSO, and assess the influence of the total volume infused the time period in which the minimum inhibitory concentration (MIC) It was more efficient and the association with DMSO increased the CIM in the synovial fluid. The animals were divided into four groups, each group received 6.6 mg gentamicin / kg per PRI, the volume to be administered, after calculating the amount of gentamicin plus or absence of DMSO was completed with Ringer\'s lactate solution with sterile until the volume in 60mL groups G60 and GD60, and up to 250 mL and G250 GD250 groups. The synovial fluid samples were collected before the start of the experiment (T0), immediately after removal of the tourniquet (T1) and after 4 (T2), 8 (T3), 12 (T4), 16 (T5) and 24 (T6) hours. The method for determination of gentamicin concentrations was employed the agar diffusion. We emphasize that the gentamicin concentrations in synovial fluid in 6.6.mg/Kg dose may be considered suitable, a period of up to 24 hours after administration. Our results indicate that the volume of 60 ml, can be considered as the ideal volume of the infusion, as well as the association of DMSO increased the gentamicin concentrations (µg / ml) in the joint of horses and possibly reduced edema formation and increases local volume.

The subject matter for this research work is the area of perioperative recovery for patients undergoing major abdominal surgery. During clinical studies we have investigated some of the factors influencing postoperative recovery as well as suggesting strategies to improve patient care. The main focus of the scientific work of this thesis is the role of intravenous fluids in the perioperative management of patients undergoing abdominal surgery. We found that restriction of intravenous fluid in the postoperative period does not significantly improve recovery in terms of gastrointestinal function (4.2 (3.2-6.9) versus 4.7 (3.7-6.1) days; p=0.80) or hospital stay (5.9 (4.0-7.9) versus 5.8 (4.1-7.3) days; p=0.90). Analysing our findings in the context of what is already known suggests that the immediate perioperative period when the effect of the metabolic-endocrine response is at its greatest is the most important period for fluid management. During this period fluid optimisation has an important role in patient recovery but following this period the body’s own homeostatic mechanisms are more able to cope with any fluid excess. We also found that using a ‘fast-track’ regime we could reduce hospital stay to levels comparable with other studies in the published literature. Our work using a multi-modal rehabilitation regime in association with both laparoscopic and open surgery suggests that it is the postoperative care package which has the more major influence on recovery. Our findings are in agreement with other small sized studies beginning to appear in the literature and indicate that further large scale studies are required to determine the role of laparoscopic surgery and any potential benefits. One of the most significant causes of morbidity for patients undergoing abdominal surgery is postoperative ileus. During the course of our studies we found that the extent of surgery and particularly handling and exposure of the intestines seems to have little effect on the duration of postoperative ileus. These findings add to the previously contradictory findings of other groups. Our experience with ‘fast-track’ postoperative programmes was also applied to liver surgery, an area where it has not previously been reported, to show that a variety of abdominal procedures may benefit from this approach. By comparing our results with series published in the medical literature we found that hospital stay can be significantly reduced (4 versus 5-8 days).

Clinical Issue Health Canada recommends exclusive breastfeeding for the first 6 months post birth and then the addition of complementary foods with breastfeeding extending to a minimum of two years. Breastfeeding initiation rates in Canada are currently at around 87% but, by one month, about 21% of women have stopped breastfeeding. Engorgement and edema in breast tissue can lead to breastfeeding challenges which may contribute to early weaning. Purpose The purpose of this pilot research study was to explore the relationship between intravenous (IV) fluids given to mothers during the peripartum period and postpartum breast or nipple swelling in the first ten days postpartum and determine if a larger study was warranted and feasible. The research question for this pilot study was, "What is the relationship between the amount of IV fluids given to labouring women and edema of the breast and areola complex experienced by breastfeeding women in the first 10 days postpartum?" Methods It is a prospective, longitudinal, observational cohort pilot study with repeated measures and a within-subjects design. Participants are first time mothers who planned to exclusively breastfeed and gave birth to a single, healthy newborn by means of a spontaneous vaginal birth, Mother and baby were discharged home together with no contraindications to exclusive unrestricted breastfeeding. Descriptive statistics are reported and linear regression analysis is used to model the relationship between IV therapy and postpartum breast edema. Results Women who received IV fluids during labour had higher levels of edema postpartum and rated their breasts as firmer as and more tender than women who did not receive IV fluids. Participants who had IV fluids appeared to be less aware of the fullness associated with lactogenesis II, and the pattern of fullness they described appeared to be related to edema noted. Participants who did not have IV fluids appeared to have unrelated patterns of fullness and edema, and therefore appeared more aware of the onset of lactogenesis II. The results support a larger study about the relationships between maternal perinatal IV fluids and breast or nipple changes.

This study was performed to compare the delivery of the antimicrobial gentamicin to the respiratory tract of adult horses following aerosol and intravenous administration. Nine adult horses were used in a crossover design. Aerosol administration of gentamicin was performed using a close fitting facemask and an ultrasonic nebulizer. Intravenous gentamicin was administered via a jugular venous catheter. Samples of pulmonary epithelial lining fluid were collected by bronchial lavage performed at 0.5, 4, 8 and 24 hours after gentamicin administration. All samples were analyzed for gentamicin concentration, and cytologic examination was performed on aliquots of bronchial lavage fluid from times 0.5, 8 and 24 hours. Comparisons were made using the Wilcoxon signed-rank test. The bronchial lavage fluid gentamicin concentration after aerosol administration was significantly greater (p<0.05) than after intravenous administration at 0.5, 4, and 8 hours. The bronchial lavage fluid total nucleated cell count increased significantly (p<0.05) from 0.5 to 24 hours following both routes of gentamicin administration, with the increase observed following aerosol administration being significantly greater (p<0.05) than that observed following intravenous administration. A significant increase in neutrophil count was detected between bronchial lavage fluid samples taken at 0.5 hours and 24 hours, regardless of route of gentamicin administration. We conclude that aerosol administration of gentamicin to the equine respiratory tract achieves bronchial lavage fluid gentamicin levels that are significantly higher than levels obtained following intravenous administration for at least the first 8 hours after administration, while inciting a mild inflammatory response.
Master of Science

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Dehydration is one of the most common disorders in the veterinary medicine. Fluid therapy is used to correction of fluid, electrolyte and acid-base disorders. This study was made to compare the effect of three electrolytic solutions administered by intravenous access. Six male adult dogs, weighting 5 and 15 kg were submitted to a dehydration protocol by restriction and polyuria. This animals were treated with three different solutions: Lactated Ringer s solution (RL), Ringer´s solution (RS) and Normal saline (0,9%) plus dextrose (5%) (GF). The variables were evaluated before (T0) and 24h after dehydration, during hydration between 6h (T2) and 12h (T3) and after 12h hydration (T4). The data were expressed in range ± standard deviation and submitted to variance analysis and non- parametric tests (p<0,05%). The dehydration protocol used in this study was enough to cause slight to moderate dehydration that was observed by the increase of packed cell volume, serum protein, urea, creatinine, albumin and osmolality that decrease after fluid therapy. It was not observed an increase of urinary density and pH become more acid during dehydration. The serum concentration of Na+, Cl-, K+, iCa++ and lactate had discreet variations between the studied times. It was observed increase of serum glucose in the GF group during rehydration phase. In the acid-base evaluation was observed an increase in pH, tCO2 and bicarbonate concentration in RL group and a slight decrease in base excess in RS group.
A desidratação é uma das desordens mais comuns na prática da clínica médicoveterinária. A fluidoterapia é utilizada para correção de déficits hidroeletrolíticos e ácido-base e, para isso, há necessidade de criteriosa escolha da solução adequada para cada tipo de desordem. No presente estudo foram comparados os efeitos de três soluções eletrolíticas, administradas por via intravenosa. Seis cães machos, adultos, pesando entre 5 e 15 Kg foram submetidos a um protocolo de desidratação por restrição e poliúria. Esses animais foram tratados com três diferentes soluções eletrolíticas: Ringer lactato (RL), Ringer simples (RS) e Glicofisiológico (GF). As variáveis foram analisadas antes (T0) e 24h (T1) após desidratação, 6h (T2) e 12h (T3) após o início da fluidoterapia e 12h após término da fluidoterapia (T4). Os dados foram expressos em média ± desvio-padrão e submetidos à análise de variância e testes não paramétricos (p<0,05%). O protocolo de desidratação utilizado neste estudo foi suficiente para produzir uma desidratação de discreta à moderada, observado pelo aumento do hematócrito, do número de eritrócitos, uréia, creatinina, proteína plasmática total, albumina e osmolalidade, que voltaram a diminuir após o início da fluidoterapia. Não foi observado aumento da densidade urinária e o pH urinário tornou-se discretamente mais ácido durante a desidratação. As concentrações séricas de Na+, Cl -, K+, iCa++ e lactato apresentaram discretas variações durante os tempos estudados. Houve aumento da glicose sérica no grupo GF durante a fase de reidratação. Na avaliação ácido-base observou-se um discreto aumento nos valores do pH, na concentração da tCO2 e do bicarbonato no grupo RL e uma diminuição da concentração de base no grupo RS.

L’optimisation hémodynamique péri-opératoire est une stratégie qui vise à maximaliser le transport artériel en oxygène et/ou le volume d’éjection systolique lors de chirurgie à risque. Ce concept a beaucoup évolué lors de ces trente dernières années, vers une approche plus simple, plus réalisable en pratique clinique et moins invasive. Les principales thérapeutiques utilisées dans les différents protocoles d’optimisation hémodynamique sont le remplissage vasculaire, l’administration d’agents inotropes et de vasopresseurs. Cependant, les conséquences physiopathologiques de l’agression chirurgicale peuvent impacter grandement les modalités d’administration et l’efficacité des thérapeutiques précitées. Dans la première étude, nous avons décrit l’impact de l’acidose respiratoire et métabolique (fréquemment rencontrées lors de chirurgie majeure et/ou de coeliochirurgie) sur l’efficacité des agents α et β-adrénergiques sur le myocarde sain de rat. Dans un deuxième travail nous avons mis en évidence que le remplissage vasculaire ne pouvait pas être guidé par des indices dynamiques de précharge dépendance lors du clampage chirurgicale de l’aorte abdominale sous-rénale, dans un modèle porcin. Enfin, dans la troisième étude, nous avons montré dans un modèle clinique, que le positionnement en décubitus ventral lors d’une chirurgie du rachis entrainait des modifications majeures des interactions cardiorespiratoires et que les indices dynamiques devaient être interprétés avec prudence pour guider le remplissage vasculaire dans ce contexte. Ces études translationnelles soulignent trois situations fréquentes impactant l’efficacité et/ou les modalités d’administration des thérapeutiques nécessaires à une optimisation hémodynamique peropératoire
The aim of perioperative haemodynamic optimization is to maximize oxygen delivery and/or stroke volume during high risk surgery. This concept has evolved during the last thirty years, to a simpler, more feasible and less invasive approach. Main treatments used in different hemodynamic optimization protocols are fluid loading, inotropes and vasopressors administration. However, pathophysiological consequences of surgical stress can greatly impact the mode of administration and the efficacy of the above therapeutics. In the first study, we described the impact of respiratory and metabolic acidosis (frequently encountered during major surgery and/or laparoscopic surgery) on the effectiveness of α and β-adrenergic agents in healthy rat myocardium. In a second work, we demonstrated that intravenous fluids cannot be guided by dynamic indices of preload dependency during surgical clamping of the infrarenal abdominal aorta in a porcine model. Finally, in the third study, we demonstrated in a clinical model, that positioning in prone position during spine surgery induced major changes in cardiorespiratory interactions and dynamic indices should be interpreted with caution to guide fluid therapy in this context. These translational studies highlight three common situations impacting the effectiveness and/or administration of therapeutic necessary for intraoperative hemodynamic optimization

博士
國立臺灣師範大學
生命科學系
105
Intravenous fluid therapy is considered the first-line drug treatment for hypovolemia, which is common in surgical patients. Appropriate intravenous fluid therapy comprises three aspects: the correct type of fluid, correct timing of fluid infusion, and correct amount of fluid infusion. If even one of these aspects is not achieved, intravenous fluid infusion may become injurious instead of being therapeutic. The aim of intravenous infusion therapy is to improve circulation during hypovolemia or hemorrhaging. Recent studies have demonstrated that microcirculatory (blood vessels <100 µm in diameter) improvement is more strongly associated with favorable outcomes than are traditional macrocirculatory indicators (e.g., mean arterial pressure and heart rate). Splanchnic microcirculatory impairment during hypovolemia may not only vary among organs (e.g., the liver, kidneys, and intestine) but is also associated with the development of multiple organ dysfunction syndrome. Only those fluid infusion therapies that improve splanchnic microcirculation can actually prevent irreversible organ damage during resuscitation from hypovolemic shock. Therefore, the first part of the first section of this dissertation addresses the development of a method for the real-time simultaneous observation of splanchnic microcirculatory changes during hemorrhagic shock by using laser speckle contrast imaging and tissue oxygen saturation in a rat model. We found that although the tissue oxygen saturation decreased homogeneously in multiple splanchnic organs, the microcirculatory blood flow was more vulnerable to hemorrhaging in the intestinal mucosa than in the liver, kidneys, and skeletal muscles. In the second part of the first section of this dissertation, we describe an exploration of the microcirculatory therapeutic effects of several common clinical intravenous fluid products, including crystalloid solutions (e.g., 0.9% saline), colloidal solutions (e.g., starch and gelatin products), and hypertonic solutions (e.g., 3% saline) during resuscitation from hemorrhagic shock. The use of different types of resuscitation fluids not only may result in variations in the extent of microcirculatory improvement but may also be associated with varying degrees of ischemia-reperfusion injury, expressed as oxidative stress. Among the abdominal organs, the kidneys are the most vulnerable to ischemia-reperfusion injury. In the clinical scenario, resuscitation from shock in critically ill patients by using colloidal fluids is associated with an increased risk of acute renal injury after treatment. This phenomenon is closely related to ischemia-reperfusion injury and oxidative stress. Because the products of oxidative stress have a very short half-life, we used an in vivo method to accurately quantitatively measure the amount of renal reactive oxygen species in rats during fluid resuscitation from hemorrhagic shock. We found that fluid resuscitation with a crystalloid solution could not restore microcirculatory blood flow in the intestinal mucosa. Instead, only colloidal and hypertonic solutions improved the microcirculatory blood flow in the intestinal mucosa. However, colloidal solutions, including starch and gelatin products, produce a considerably larger amount of renal reactive oxygen species than do crystalloid and hypertonic solutions. This phenomenon may be associated with acute renal injury after colloidal fluid resuscitation, as reported in the clinical literature. In the first section of this dissertation, we conclude that the microcirculatory blood flow in the intestinal mucosa is most vulnerable to hemorrhagic shock. Furthermore, both colloidal and hypertonic solutions can restore the intestinal microcirculatory blood flow during hemorrhagic shock. However, fluid resuscitation with colloidal solutions may result in significant ischemic-reperfusion injury, which is indicated by the production of a large number of renal reactive oxygen species. The accurate determination of the time for administering an intravenous infusion is clinically challenging. At present, the most precise indicators of the time for administering fluid infusion may be dynamic fluid responsiveness parameters. These indicators reflect the interaction between the heart and lungs during mechanical ventilation. The lower the blood volume, the greater the variations in hemodynamic parameters during the respiratory cycle are. Therefore, when the dynamic fluid responsiveness parameters are higher than their threshold values, a fluid challenge is likely to considerably increase the cardiac output (this phenomenon is called “fluid responsiveness”), thereby improving the circulation. However, the threshold values of the dynamic fluid responsiveness parameters are based on patients with normal vascular tones. Certain patient groups are characterized by an abnormal vascular tone, for instance, patients with live cirrhosis have reduced vascular resistance because vasodilation-inducing substances cannot be metabolized as a result of end-stage liver disease. In the second section of this dissertation, we describe an investigation on the accuracy of three dynamic fluid responsiveness parameters, namely pulse pressure variation, stroke volume variation, and the plethysmographic variability index, in patients with liver cirrhosis. We found that although these three indicators were less accurate for predicting fluid responsiveness in common surgical patients, they were sufficiently precise to predict fluid responsiveness in patients with liver cirrhosis. Therefore, clinicians can determine the correct time for fluid administration to patients with liver cirrhosis using these indicators. In the final section of this dissertation, we clarify how to determine the correct amount of intravenous fluid for infusion, particularly with regard to vital organs. If a vital organ does not have the risk of ischemia and although intravenous infusion can improve cardiac output, excessive fluid infusion may lead to tissue edema and injury. For brain surgery, such a clinical judgment is challenging because the brain tissue has high metabolic and perfusion demands, particularly during surgery. However, excessive fluid infusion may also result in brain edema, poor outcomes, and neuronal injury. Dynamic fluid responsiveness parameters are characterized with a “gray zone.” In this interval, the lower and upper limit cutoffs respectively represent a high specificity and high sensitivity of fluid responsiveness. In an intraoperative fluid strategy targeting the upper cutoff of the gray zone, the fluid challenge highly specifically increases cardiac output without the risk of tissue edema, but the sensitivity is low; hence, a restrictive fluid balance may exist. By contrast, in a fluid strategy targeting the lower cutoff of the gray zone, a higher intraoperative cardiac output may be achieved after the fluid challenge, but the risk of tissue edema simultaneously increases. With regard to brain surgery, we investigated whether different amounts of fluid infused during intraoperative fluid challenges favored the upper or lower cutoffs in the gray zone. The results revealed that patients receiving a fluid strategy targeting the lower cutoff of the gray zone had a shorter intensive care unit stay, fewer postoperative neurological events, a superior discharge functional status, less intraoperative lactate accumulation, and lower postoperative serum neuronal injury protein expression than did patients receiving a fluid strategy targeting the upper cutoff of the gray zone. We confirmed that for patients undergoing brain surgery, the intraoperative fluid strategy should aim to maintain and increase cardiac output as much as possible. The importance of intravenous fluid therapy to surgical conditions is being increasingly emphasized in modern medicine. In summary, we investigated the pathological microcirculatory changes in multiple splanchnic organs during hemorrhagic shock in a rat model and confirmed the therapeutic effects of hypertonic saline and colloidal solutions on the restoration of intestinal mucosal microcirculatory blood flow. In addition, in vivo induction of renal reactive oxygen species by colloid solutions is reported for the first time, and this phenomenon may be associated with acute kidney injury in critically ill patients after fluid resuscitation with colloidal solutions. For further clinical applications, we observed that dynamic fluid responsiveness parameters enable clinicians to accurately determine the timing of fluid infusion not only for general surgical patients but also for patients with liver cirrhosis with altered vascular tones. Finally, we confirmed that an intraoperative fluid strategy targeting the elevation of cardiac output may be more beneficial than a restrictive strategy to patients undergoing brain tumor resection surgery. As long as the fluid therapy is based on the concept of administering the correct type of fluid at the correct time and in the correct amount, opportunities to further improve the clinical care of surgical patients are numerous. Our research begins from this perspective, and we would like to further investigate fluid therapy. Key words: splanchnic microcirculation、colloid solution、hypertonic solution、oxidative stress、liver cirrhosis、dynamic fluid responsiveness parameter、brain surgery

Obstructive sleep apnea (OSA) severity is strongly associated with the degree of overnight peripharyngeal fluid accumulation. We hypothesized that intravenous fluid loading would cause upper airway (UA) narrowing or increase the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index; AHI). We employed a controlled, randomized double-crossover experiment in 9 healthy men aged 23-46 years. In the control, subjects were administered approximately 80 ml of normal saline intravenously during sleep. In the intervention, subjects were administered approximately 1850 ml of saline during sleep while wearing compression stockings to localize fluid rostrally. The intervention induced nuchal fluid accumulation, resulting in an increase in neck circumference (+0.1 cm during control, +0.6 cm during intervention, P< 0.01 ) and a decrease in UA cross-sectional area (-0.08 cm2 during control, -0.43 cm2 during intervention, P = 0.023). Although the intervention did not increase the AHI (control AHI = 19.5, intervention AHI = 30.3, P = 0.249), the AHI during the intervention correlated with age (r = 0.8, P < 0.01). Thus, intravenous saline loading during sleep can narrow the UA, which in older men may induce or worsen OSA. Further studies are needed to test this hypothesis.

abstract: Achieving effective drug concentrations within the central nervous system (CNS) remains one of the greatest challenges for the treatment of brain tumors. The presence of the blood-brain barrier and blood-spinal cord barrier severely restricts the blood-to-CNS entry of nearly all systemically administered therapeutics, often leading to the development of peripheral toxicities before a treatment benefit is observed. To circumvent systemic barriers, intrathecal (IT) injection of therapeutics directly into the cerebrospinal fluid (CSF) surrounding the brain and spinal cord has been used as an alternative administration route; however, its widespread translation to the clinic has been hindered by poor drug pharmacokinetics (PK), including rapid clearance, inadequate distribution, as well as toxicity. One strategy to overcome the limitations of free drug PK and improve drug efficacy is to encapsulate drug within nanoparticles (NP), which solubilize hydrophobic molecules for sustained release in physiological environments. In this thesis, we will develop NP delivery strategies for brain tumor therapy in two model systems: glioblastoma (GBM), the most common and deadly malignant primary brain tumor, and medulloblastoma, the most common pediatric brain tumor. In the first research chapter, we developed 120 nm poly(lactic acid-co-glycolic acid) NPs encapsulating the chemotherapy, camptothecin, for intravenous delivery to GBM. NP encapsulation of camptothecin was shown to reduce the drug’s toxicity and enable effective delivery to orthotopic GBM. To build off the success of intravenous NP, the second research chapter explored the utility of 100 nm PEGylated NPs for use with IT administration. Using in vivo imaging and ex vivo tissue slices, we found the NPs were rapidly transported by the convective forces of the CSF along the entire neuraxis and were retained for over 3 weeks. Based on their wide spread delivery and prolonged circulation, we examine the ability of the NPs to localize with tumor lesions in a leptomeningeal metastasis (LM) model of medulloblastoma. NPs administered to LM bearing mice were shown to penetrate into LM mets seeded within the meninges around the brain. These data show the potential to translate our success with intravenous NPs for GBM to improve IT chemotherapy delivery to LM.
Dissertation/Thesis
Doctoral Dissertation Biomedical Engineering 2018

碩士
中臺科技大學
醫療暨健康產業管理系碩士班
103
Abstract Backgrounds and Purpose: There has been a substantial increase of head and neck cancer patients in Taiwan over past few years. Free flap reconstruction has become a mainstream surgery for prolonging patient’s life and enhancing the quality of medical prognosis. One of the most important roles in time consuming surgery is an anesthetic technique that stabilizes hemodynamics during operation and reduces the complications after surgery. This study is primarily concerned with the infusion volumes of surgery and post-operative complications at different methods of anesthesia for free flap surgery. Methods: This study employed a retrospective design. Subjects were the head and neck cancer patients at a teaching medical center in central Taiwan who received “free flap reconstruction surgery”. A total of 60 patients were selected during November 2013 to April 2014 (30 of the subjects were treated inhalation anesthesia, and 30 subjects were treated intravenous anesthesia). The primary criterion for eliminating subjects was patients who had lung disease, uremia, ASA III, ASA IV, and age over 60 years old. The study variables are based on reviewing the medical records and anesthesia record sheets in order to obtain the basic patient information, diagnosis, treatments, operations, prognosis (pulmonary complications, infections, bleeding, and days in hospital), and anesthesia-related information (such as anesthesia methods, infusion volumes…etc). The analysis used the SPSS 18.0 statistical software package including Chi-square, independent t-test and others to conduct descriptive and inferential statistical analysis. Results: The results showed that there were no statistically significant differences between two anesthesia methods in patient’s characteristic of gender, ASA classifications, height, ages, weights and Body Mass Index (BMI); no significant differences in hypertension or diabetes (p> 0.05); no significant differences in treatments of electrotherapy or chemotherapy before surgery. However, there was a significantly associated between two anesthesia methods in postoperative pulmonary complications. Besides, the operation time, infusion volumes, and urine amounts were significantly differences (p< 0.05); but the losses of blood volume and central venous pressure showed no significant differences (p> 0.05). In addition, the durations of ventilator support and the days of stay in ICU between two different anesthesia methods were no noticeable differences (p>0.05), but the days stay in hospital has significant differences (p<0.05). Conclusions: The findings indicated that postoperative pulmonary complications are less likely to happen in free flap surgery patients who treated with total intravenous anesthesia. We also found that the amount of infusion volume for total intravenous anesthesia was significantly lower than the inhaled anesthesia. It is necessary to have professional anesthesia care for maintaining the fluid volumes to stabilize the patient’s hemodynamics in the time-consuming surgery. This study concluded that the total intravenous anesthesia method is the best valuable choice during free flap surgery.

碩士
國立中興大學
生命科學院碩士在職專班
100
Background: Human amniotic fluid mesenchymal stem cells (AFS) have been shown to promote peripheral nerve regeneration. The expression of stromal derived factor 1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, we investigated the feasibility of intravenous administration of AFS according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model. Material and Methods: Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of three groups: Group I: crush injury as the control; Group II: crush injury and intravenous administration of AFS (5x106 cells for 3 days) immediately after injury (early administration); and Group III: crush injury and intravenous administration of AFS (5x106 cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α , neurotrophic factors, and the distribution of AFS in various time profiles were also assessed. Results: SDF-1α increased the migration and wound healing of AFS in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10-14 days either at nerve or muscle, and this increased expression paralleled the expression of its receptor CXCR-4. Most AFS was distributed to the lung during early or late administration. Significant deposition of AFS in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group. Conclusion: AFS cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFS paralleled the expression profiles of SDF-1α and its receptor CXCR-4 either in muscle or nerve. AFS administration led to improvements of neurobehavior and expression of regeneration markers. Intravenous administration of AFS may be a promising alternative treatment strategy in peripheral nerve disorder.

Thesis (Ph. D.)--University of Georgia, 2002.
Directed by William Vincent Caufield. Includes articles published in Chromatographia, and an article accepted by Journal of liquid chromatography and related technologies. Includes bibliographical references.

碩士
國立雲林科技大學
機械工程系碩士班
89
ABSTRACT Hypovolemic shock, both traumatic and non-traumatic, is very harmful to tissue cells. Cell damage soon occurs if the deficiency of oxygen and nutrition from hypoperfusion cannot be corrected in time, followed by organ dysfunction, and even death. Permanent sequelae are common in the one who is able to escape from death after treatment. Fluid resuscitation in time is therefore essential to reduce the morbidity and thus the mortality in patients with hypovolemic shock. Fluid therapy is one of the major improvements in current medicine. It is very important to correct the hypovolemia soon, especially when the hemorrhage has been controlled. Although there have been several machines to provide efficient fluid resuscitation with precision. They are huge, heavy and expensive. It is impossible to have such equipment in every hospital and ambulance or on the scene of disaster. Different peripheral venous and central venous catheters were utilized for fluid resuscitation for years, however, which one is better remains controversial. Scientific analysis on the hydrodynamic performance of daily used infusion devices with various fluids remains not available. This experiment module is designed with consideration of the state of art about resuscitation and the science of fluid mechanics. This objective of this study is to measure the infusion flow rate (F) for 16Ga peripheral venous and central catheters with various fluids for resuscitation and to evaluate the hydrodynamic performance of the tested infusion sets. The resuscitation fluids, including crystalloids, colloids and red blood cells were tested in the experimental module under the conditions of gravity-driven and pressure-driven infusions. Water was also tested to verify the accuracy of the instrumentation. The test results indicate that the relationship of flow rate and infusion pressure (P) could be expressed by a mathematical model, . The resistance coefficients are correlated and tabulated for each fluid and catheter. Each fluid flowing into different catheter will have individual values of RL and RT depending on the viscosity for each fluid and the frictional characteristic for each catheter. The test results indicate that the central catheter has a poor infusion flow rate than the peripheral catheter due to its longer catheter length and smaller catheter diameter. Furthermore, the f friction factors were correlated for the plastic tubing and the central catheter; K loss factors were also obtained for the drip chamber and peripheral venous catheter. Therefore, using the modified Bernoulli equation with the empirically obtained f and K factors, the required infusion pressure at a giving flow rate can be predicted for each fluid and a particular catheter. The predictions of the modified Bernoulli equation show very good agreement with the present infusion pressure data with a mean deviation of 8.35% for peripherial catheter and 11.30% for central catheter. The utilization of the modified Bernoulli equation should be very helpful for efficient fluid resuscitation in hospital, ambulance and on the scene of disaster. Key words: Hypovolemia, Shock, Fluid Resuscitation, Infusion set and Catheter