Metaanálisis de los efectos del suero salino en la mortalidad en cuidados intensivos / Meta-analysis of the effects of normal saline on mortality in intensive care

Introducción y objetivo: Evaluar, mediante un metaanálisis, el efecto del suero salino sobre la mortalidad en los pacientes de cuidados intensivos, cuando se compara su uso con el de cristaloides balanceados. Material y método: Se ha realizado un metaanálisis de ensayos clínicos controlados, aleatorizados y estudios prospectivos secuenciales en el tiempo, publicados, que evaluaron la mortalidad del suero salino en enfermos ingresados en unidades de cuidados intensivos. Se llevó a cabo una búsqueda electrónica en Medline, Embase, biblioteca Cochrane, ISI Proceedings y Web of Science y una búsqueda manual sobre las referencias seleccionadas. La extracción de datos fue realizada de forma independiente por 2 investigadores. Las discrepancias se resolvieron por consenso en el grupo de trabajo. El cálculo de la OR y su intervalo de confianza se realizó ponderando por el inverso de la varianza. La heterogeneidad se evaluó mediante I2. El sesgo de publicación se valoró mediante funnel plot y test de Egger. Resultados: Se seleccionaron 8 artículos para el metaanálisis de mortalidad, que incluían un total de 20.684 pacientes. Se objetivó una asociación entre el uso de suero salino y la mortalidad en los enfermos de cuidados intensivos (OR 1,0972; IC 95%:1,0049-1,1979) cuando se comparaba con el uso de cristaloides balanceados. No se encontró evidencia de sesgo de publicación (prueba de Egger p=0,5349). En el análisis de sensibilidad ninguno de los estudios modificó sustancialmente el resultado global si se eliminaba del metaanálisis. Conclusiones: Es posible que exista un aumento de la mortalidad asociada al empleo de suero salino en los pacientes ingresados en cuidados intensivos cuando se compara con el empleo de cristaloides balanceados

Introduction and objective: To evaluate, by means of a meta-analysis, the effect of normal saline on mortality in intensive care patients, when compared with the use of balanced crystalloids. Material and method: Published controlled clinical trials, randomised and sequential prospective studies in time, evaluating the mortality when physiological saline was used in patients admitted to intensive care units. Electronic search was performed in Medline, Embase, Cochrane Library, ISI Proceedings, and Web of Science, as well as a manual search of selected references. An independent evaluation was performed by 2 investigators. Discrepancies were resolved by consensus in the working group. Contingency tables were performed, and the OR with confidence intervals of each study were obtained. Heterogeneity was assessed by I2. Publication bias was assessed using funnel plot and Egger test. Results: A total of 8 articles were selected for the meta-analysis of mortality, which included a total of 20,684 patients. A significant association was observed between the use of saline and mortality in intensive care patients (OR 1.0972; 95% CI 1.0049-1.1979), when compared to the use of balanced crystalloids. No statistical evidence of publication bias (Egger, P=.5349) was found. In the sensitivity analysis, none of the studies substantially modified the overall outcome if it was eliminated from the meta-analysis. Conclusions: There may be an increase in mortality associated with the use of saline in patients admitted to intensive care when comparing with the use of balanced crystalloids

Analyzing the efficacy of frequent sodium checks during hypertonic saline infusion after elective brain tumor surgery.

OBJECTIVE: To assess the utility of frequent sodium checks (every 6h) in patients receiving hypertonic saline (HS) after elective brain tumor surgeries. PATIENTS AND METHODS: A single-institution retrospective review of patients having undergone elective craniotomies for brain tumors and treated with postoperative continuous intravenous infusions of 3% HS was performed. Changes in serum sodium values were analyzed at different time points. The rates of <12.5, 25, and 50cc/h infusions were also examined. Healthcare cost analysis was performed by extrapolating our cohort to the total number of craniotomies performed in the United States. RESULTS: No significant differences among sodium values checked between 0 to 4, 4-6, 6-8, 8-10, and >10h were observed (P=.64). In addition, no differences in serum sodium values among the rates of <12.5, 25, and 50cc/h were found (P=.30). No patients developed symptoms of acute hypernatremia. CONCLUSIONS: Serum sodium values did not significantly change more than 10h after infusion of HS. Further studies are needed to determine the optimal frequency of routine sodium checks to increase the quality of care and decrease healthcare costs.

Duration of action of hypertonic saline on mucociliary clearance in the normal lung.

Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases. Before moving toward testing the clinical benefits of HS for non-CF indications, we sought to assess the duration of pharmacodynamic effects of HS in healthy subjects by performing radiotracer clearance studies at baseline, 30-min post-HS administration, and 4-h post-HS administration. Indeed, acceleration of MC was observed when measured 30 min after HS inhalation. This acceleration was most pronounced in the first 30 min after inhaling the radiotracer in the central lung region (mean Ave30Clr = 15.5 vs. 8.6% for 30-min post-HS treatment vs. mean baseline, respectively, P < 0.005), suggesting that acute HS effects were greatest in the larger bronchial airways. In contrast, when MC was measured 4 h after HS administration, all indices of central lung region MC were slower than at baseline: Ave30Clr = 5.9% vs. 8.6% (P = 0.10); Ave90Clr = 12.4% vs. 16.8% (P < 0.05); clearance through 3 h = 29.4 vs. 43.7% (P < 0.002); and clearance through 6 h = 39.4 vs. 50.2% (P < 0.02). This apparent slowing of MC in healthy subjects 4-h post-HS administration may reflect depletion of airway mucus following acute HS administration.

Correlation of measured and calculated serum osmolality during mannitol or hypertonic saline infusion in patients after craniotomy: a study protocol and statistical analysis plan for a randomised controlled trial.

INTRODUCTION: Brain oedema is a major complication after craniotomy. Hyperosmolar agents have been used as the medical treatment for this condition. Measurement and estimation of serum osmolality during hyperosmolar agent infusion is of clinical importance to evaluate clinical efficacy, adjust dosage and avoid side effects. However, several studies have shown that calculated serum osmolality may lead to a systematic bias compared with direct measurement. In the present study, mannitol or hypertonic saline (HS) will be used in patients after elective craniotomy. We aim to determine the accuracy of serum osmolality estimation during the application of hyperosmolar agent. METHODS AND ANALYSIS: The study is a prospective, randomised, double-blinded, controlled, parallel-group design. Adult patients requiring the use of hyperosmolar agents for the prevention or treatment of postoperative brain oedema are enrolled and assigned randomly to one of the two treatment study groups, labelled as 'M group' and 'HS group'. Patients in the M and HS groups receive intravenous infusion of 125 mL of either 20% mannitol or 3.1% sodium chloride solution, respectively. Data will be collected immediately before the infusion of study agents, 15, 30, 60, 120, 240 and 360 min after the start of infusion of experimental agents, which includes serum osmolality, concentration of serum sodium, potassium, urea and glucose. Serum osmolality will be measured by means of freezing point depression. Estimated serum osmolality will also be calculated by using four formulas published previously. Osmole gap is calculated as the difference between the measured and the estimated values. The primary endpoint is the correlation of measured and estimated serum osmolality during hyperosmolar agent infusion. ETHICS AND DISSEMINATION: The study was approved by the International Review Board (IRB) of Beijing Tiantan Hospital, Capital Medical University. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02037815.

Estudio sobre la eficacia y utilidad de la solución salina hipertónica al 3 porciento en la bronquiolitis aguda del lactante hospitalizado / Nebulized 3 percent hypertonic saline solution in hospitalized infants with acute bronchiolitis: case-control study on the utility and effectiveness

Objetivo: estudiar la utilidad de la solución salina hipertónica (SSH) al 3% inhalada en el tratamiento de la bronquiolitis aguda (BA) del lactante hospitalizado. Pacientes y métodos: estudio de casos y controles realizado con 639 pacientes de edad inferior a siete meses e ingresados con diagnóstico de BA, primer episodio, durante tres periodos estacionales consecutivos, en la sección de lactantes de un hospital pediátrico de Madrid (España). Los pacientes que recibieron como tratamiento, durante los dos primeros periodos estacionales, suero salino fisiológico (SSF) inhalado con o sin medicación se consideraron el grupo control y los pacientes que recibieron, durante el tercer periodo estacional, suero salino hipertónico al 3% inhalado con o sin medicación se consideraron como casos. Los días de hospitalización y las horas de oxigenoterapia fueron utilizados como medidas de resultado. Resultados: de la totalidad de los niños estudiados, 460 recibieron SSF inhalado, y 179 recibieron SSH al 3%. En el grupo que recibió SSF, la estancia media en el hospital fue de 5,16 días (intervalo de confianza del 95% [IC 95%]: 4,78-5,56) y el tiempo medio de oxigenoterapia fue de 57,34 (IC 95%: 52,93-61,75) frente a 4,90 días (IC 95%: 4,64-5,07) y 67,53 horas (IC 95%: 60,36-74,69), respectivamente, en el grupo tratado con SSH. Estos resultados no alcanzan significación estadística. Los pacientes con estudio positivo de virus respiratorio sincitial (VRS) en aspirado nasofaríngeo y que recibieron SSF necesitaron menos horas de oxígeno de manera significativa (p=0,004), así como aquellos que tenían edad <3 meses (p=0,007). Conclusiones: los resultados obtenidos muestran que la SSH al 3% inhalada no resulta eficaz para reducir la estancia hospitalaria ni el tiempo de oxigenoterapia en los pacientes con BA; además, en los niños menores de tres meses y con estudio positivo de VRS en aspirado nasofaríngeo la aplicación de SSF inhalado consiguió una necesidad menor de horas de oxígeno (AU)

Objective: to study the utility of nebulized 3% hypertonic saline solution (HSS) in hospitalized infants with acute bronchiolitis. Patients and methods: case-control studies accomplished on 639 patients of age less than 7 months old and hospitalized with the diagnosis of acute bronchiolitis, first episode, during 3 consecutive seasons in a pediatric department in Madrid. The patients who received 0.9% saline solution (FSS), with or without medication, during the 2 first seasons were considered the control group and the patients who received, the last season period, nebulized 3% hypertonic saline solution were considered the cases group. The days of hospitalization and the hours of oxygen therapy were used as the result measurement. Results: from the total of the studied children, 460 received 0.9% saline solution and 179 received 3% hypertonic saline solution. In the group receiving FSS the average stay in hospital was 5.16 days (95% confidence interval [95% CI] 4.78-5.56) and the average time of oxygen therapy was 57.34 hours (95% CI 52.93-61.75) opposite to 4.90 days (95% CI 4.64-5.07) and 67.53 hours (95% CI 60.36- 74.69) respectively in the group that received HSS. There was no significant difference between the groups. The patients who received FSS and were positive for VRS and also patients less than 3 months old, showed a significant reduction in the oxygen therapy hours (p= 0.004 and p= 0.007 respectively). Conclusions: results show that 3% hypertonic saline solution has not been effective in reducing hospital stay or length of oxygen therapy in patients with acute bronchiolitis; but nebulized 0,9% saline solution in children with age <3 months and positive study of respiratory syncitial virus in nasopharyngeal aspirate showed a reduced need of hours of oxygen (AU)

Acción antibacteriana de pastas de hidróxido de calcio frente a Enterococcus faecalis / Antibacterial effciacy by calcium hydroxide pastes on Enterococcus faecalis

Objetivo. Se evaluó in vitro la actividad antibacteriana de pastas de Ca (OH)2 frente a Enterococcus faecalis. Material y método. Las pasta usadas fueron: 1-Ca(OH)2 con solución salina, 2-Ca(OH)2 con clorhexidina (CHX) 0,2% y 3-Ca (OH)2 con propilenglicol. Se trabajó con 6 tubs experimentales y un tubo control de crecimiento bacteriano y se realizó una curva de muerte, evaluándolas a diferentes tiempos 0,1,2 y 5 horas y 1, 7 y 14 días. Los datos se analizaron con ANOVA. Resultados y conclusiones. Ca (OH)2 con CHX 0,2% produjo inhibición total de Enterococcus faecalis a la hora de permanencia en contacto con el microorganismo, manteniéndose este efecto durante los 14 días. La pasta de Ca (OH)2 con propilenglico inhibió al microorganismo durante la 1º hora, sin evidenciarse diferencias con la pasta 2 (p>0,05), manteniéndose este efecto durante 5 horas, luego hubo recrecimiento bacteriano. La pasta de Ca(OH=2 con solución salina inhibió al Enterococcus faecalis a partir del día 1 hasta el día 14 (AU)

Objective. The aim of this study was to evaluate the antimicrobial effects of calcium hydroxide pastes on Enterococcus faecalis. Material and methods. The pastes evaluated were: 1-calcium hydroxide with saline solution, 2-calcium hydroxide with chlorhexidine (CHX) 0,2% and 3-calcium hydroxide with propileneglicol. Six experimental tubes and one control tube were prepared and incubated for 0, 1, 2, 5 hours, 1, 7 and 14 days. The curves death were made. The data was analyzed with ANOVA test. Results and Conclusions. Ca (OH)2 with CHX 0,2% paste inhibited Enterococcus faecalis at 1 hour and maintained this effect over 14 days. Ca(OH)2, with propileneglicol had inhibitory effect at 1 hour, showing no significant difference with paste 2 (p>0,05). Paste 3 maintained inhibitory action for 5 hours, then microorganism grow again. Ca(OH)2 with saline solution paste inhibit Enterococcus faecalis after 1 day of contact. This effect continue to 14th day. Ca(OH)2 with CHX 0,2% and Ca(OH)2 with propileneglicol pastes were effective in 1 hour time (p<0,05). Only the pastes 1 and 2 maintained inhibitory action for 14 days (AU)

Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema.

OBJECTIVE: To characterize membrane conductivity by applying mathematical modeling techniques and immunohistochemistry and to localize and predict areas of the bowel where aquaporins may be associated with edema resolution/prevention associated with hypertonic saline. Intestinal edema induced by resuscitation and mesenteric venous hypertension impairs intestinal transit/contractility. Hypertonic saline decreases intestinal edema and improves transit. Aquaporins are water transport membrane proteins that may be up-regulated with edema and/or hypertonic saline. DESIGN: Laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague Dawley rats, weighing 270 to 330 g. INTERVENTIONS: Rats were randomized to control (with and without hypertonic saline) and mesenteric venous hypertension with either 80 mL/kg normal saline (RESUS + VH + VEH) or 80 mL/kg normal saline with hypertonic saline (RESUS + VH + HTS). After 6 hrs, intestinal wet/dry ratios, urine output, peritoneal fluid, and intraluminal fluid were measured. Hydraulic conductivity was calculated from our previously known and published pressure-flow data. The cDNA microarray, Western blot, polymerase chain reaction, and immunohistochemistry studies were conducted for candidate aquaporins and distribution in intestinal edema resolution. MEASUREMENTS AND MAIN RESULTS: Hypertonic saline decreased edema and increased urine, intraluminal, and peritoneal fluid volume. RESUS + VH favors fluid flux into the interstitium. Hypertonic saline causes increased hydraulic conductivity at the seromuscular and mucosal surfaces at the same time limiting flow into the interstitium. This is associated with increased aquaporin 4 expression in the intestinal mucosa and submucosa. CONCLUSIONS: Hypertonic saline mitigates intestinal edema development and promotes fluid redistribution secondary to increased membrane conductivity at the mucosal and seromuscular surfaces. This is associated with up-regulation of aquaporin 4 gene expression and protein. Aquaporin 4 may be a useful therapeutic target for strategies to enhance edema resolution.

Respuestas cardiovasculares al NaCl hipertónico inyectado en la región anteroventral del tercer ventrículo de ratas con hipertensión e insulinorresistencia inducidas por fructosa / Cardiovascular responses to hypertonic NaCl injection into the anteroventral third ventricle region in rats with fructose-induced hypertension and insulin resistance

Introducción y objetivos. Evaluar la respuesta simpática desencadenada por microinyección de NaCl 1,5 mol (2 µl) en la región anteroventral del tercer ventrículo cerebral de ratas alimentadas con fructosa a largo plazo. Métodos. Se usaron ratas macho de la cepa Sprague Dawley. El grupo control (n = 12) recibió dieta convencional y el grupo experimental, fructosa al 60% en comida convencional (n = 12) durante 6 meses. Resultados. La fructosa produjo aumento de peso corporal, hipertrigliceridemia, hipercolesterolemia, hiperuricemia, hiperinsulinemia e hipertensión arterial, sin cambios en la frecuencia cardiaca basal. La respuesta hipertensiva por microinyección de 2 µl de NaCl 1,5 mol/l en la región anteroventral del tercer ventrículo cerebral (AV3V) fue mayor en las ratas alimentadas con fructosa; la presión arterial sistólica (PAS) aumentó 44,64, ± 3,6 mmHg y la diastólica (PAD) 19,9 ± 2,4 mmHg (p < 0,01); en el grupo control la PAS aumentó 28,33 ± 3,10 mmHg y la PAD 13,0 ± 1,9 mmHg sobre los valores basales (p < 0,01). La frecuencia cardiaca aumentó 23,0 ± 5,0 lat/min en el grupo control y 66,2 ± 8,4 lat/min (p < 0,01) en el grupo con fructosa. Conclusiones. La administración de fructosa a largo plazo en la dieta produce hiperreactividad simpática del área AV3V al cloruro de sodio hipertónico, asociada con el desarrollo de hipertensión y resistencia insulínica (AU)

Introduction and objectives. To investigate the hemodynamic sympathetic response evoked by NaCl microinjection into the third ventricle anteroventral brain area (AV3V) in rats long-term fed with high fructose diet. Methods. Twelve male rats received 60% fructose enriched diet for 6 months. Control rats (n=12) received regular diet. Results. Fructose diet increased (P<.01) body weight; plasma glucose, triglycerides; cholesterol, insulin; systolic (SBP) and diastolic blood pressure (DBP). Basal heart rate (HR) did not change. AV3V microinjection of 2 µL of hypertonic 1.5 M NaCl in fructose fed rats increased SBP 44.64(3.6) mm Hg, DBP 19.9(2.4) mm Hg and HR 66.2(8.4) beats/min over basal values (P<.01). In control rats, smaller responses were observed, SBP increased 28.33(3.10) mm Hg, DBP 13.0(1.9) mm Hg and HR 23.0(5.0) beats/min over basal values (P<.01). Conclusions. Long-term fructose diet in rats induces cardiovascular hyperactivity of AV3V neurons to sodium chloride, and is associated to hypertension and insulin-resistance (AU)

Mechanism and rate of middle ear fluid absorption.

Several mechanisms have been suggested to explain the clearance of fluids from the middle ear. These include a pumping action through the eustachian tube, mucociliary beating through the tube, outflow of water to the blood due to osmotic gradients and an active Na(+) transport driving water absorption. In order to assess these mechanisms, the middle ear cavity of paralyzed, ventilated (eustachian tube occluded) guinea pigs was filled with fluids varying in osmotic pressure (hypotonic, isotonic, hypertonic) to which a vertical tube was attached. The change in height of fluid in the tube was taken as a measure of changes in middle ear fluid volume. A greater fluid volume reduction was seen with the hypotonic (1/5 saline) solution. A small volume increase was observed with the hypertonic solution. These results provide evidence that in these experimental conditions, water absorption due to osmotic gradients can contribute to middle ear fluid clearance.

Isotonic and hypertonic saline droplet deposition in a human upper airway model.

The evaporative and hygroscopic effects and deposition of isotonic and hypertonic saline droplets have been simulated from the mouth to the first four generations of the tracheobronchial tree under laminar-transitional-turbulent inspiratory flow conditions. Specifically, the local water vapor transport, droplet evaporation rate, and deposition fractions are analyzed. The effects of inhalation flow rates, thermodynamic air properties and NaCl-droplet concentrations of interest are discussed as well. The validated computer simulation results indicate that the increase of NaCl-solute concentration, increase of inlet relative humidity, or decrease of inlet air temperature may reduce water evaporation and increase water condensation at saline droplet surfaces, resulting in higher droplet depositions due to the increasing particle diameter and density. However, solute concentrations below 10% may not have a very pronounced effect on droplet deposition in the human upper airways.

Soluções salinas tópicas nasais / Topical saline nasal solutions

A irrigação nasal é freqüentemente indicada como medida adjuvante no tratamento de várias afecções que acometem a cavidade nasal e os seios paranasais. Esta revisão foi realizada com o intuito de examinar as evidências recentes quanto à eficácia e benefícios da utilização da solução salina nasal no tratamento das afecções da cavidade nasal e dos seios paranasais. Estudos randomizados e controlados com a utilização de solução nasal hipertônica em pacientes com rinossinusite aguda, crônica, rinite alérgica e sintomas nasais crônicos, têm mostrado melhora significante dos sintomas nasais, escores de qualidade de vida, diminuição da utilização de antibióticos e spray nasal. A irrigação nasal é um procedimento simples, barato, promove alívio dos sintomas associados às doenças nasais e reduz a utilização de medicações.

The effect of 7.2% hypertonic saline solution on the duration of sodium gradient between the cerebrospinal fluid and the venous circulation in the dog.

To determine the duration of water movement from cerebrospinal fluid (CSF) into venous blood by the infusion of 7.2% hypertonic saline solution (HSS), the sodium gradient between venous blood and CSF were examined. Venous sodium concentrations remained higher than that in CSF for duration of 60 min following HSS infusion. By 90 min, the CSF sodium concentration reached the equilibrium with venous sodium concentration. Those data suggests that the duration of time during which water moved from CSF into capillaries in brain by the gradient of sodium concentration was less than 90 min.

Osmotic therapy: fact and fiction.

This review examines the available data on the use of osmotic agents in patients with head injury and ischemic stroke, summarizes the physiological effects of osmotic agents, and presents the leading hypotheses regarding the mechanism by which they reduce ICP. Finally, it addresses the validity of the following commonly held beliefs: mannitol accumulates in injured brain; mannitol shrinks only normal brain and can increase midline shift; osmolality can be used to monitor mannitol administration; mannitol should be not be administered if osmolality is >320 mOsm; and hypertonic saline is equally effective as mannitol.

Natriuresis and the extracellular volume expansion by hypertonic saline.

BACKGROUND: The mechanisms governing the duration of the extracellular fluid volume (ECF) expansion as a result of intravenous infusion of hypertonic saline solution are poorly understood. We hypothesized that the duration is closely related to the sodium excretion. MATERIALS AND METHODS: Six conscious splenectomized ewes with a mean body weight of 30 kg were given an intravenous infusion of 4 ml x kg(-1) of 7.5% saline solution on two occasions, one over a period of 5 min and another over a period of 20 min. Mass balance and volume kinetic calculations of the distribution and elimination of fluid were performed after repeated sampling of the plasma sodium concentration and the urinary excretion of water and sodium during 3 h. RESULTS: On considering the addition of sodium to and its excretion from the body, the plasma sodium concentration indicated a 10% dilution of the extracellular space. The volume expansion decayed at an average rate of 20% of the volume expansion per hour, which, however, varied greatly in the animals, depending on their capacity to excrete sodium. After 1 h, increasing natriuresis promoted translocation of water into the cells, which amounted to 25-35% of the total elimination. Computer simulations indicated that tripled natriuresis (up to approximately 750 mmol l(-1)) would increase the rate of elimination to 45% of the volume expansion per hour. CONCLUSION: The sodium excretion was inversely proportional to the duration of the extracellular volume expansion by 7.5% saline.

Aerosol deposition and clearance measurement: a novel technique using dynamic SPET.

Planar gamma camera scintigraphy is a well-established technique for characterising the deposition and clearance of radiolabelled aerosols. While single-photon emission tomography (SPET) can offer superior assessment of radioaerosol deposition and better differentiation between peripheral and central deposition, the long acquisition times of single-headed SPET have largely prevented its use for measuring clearance or deposition of fast-clearing radioaerosols. This study investigated the feasibility of fast dynamic SPET imaging (1 min/frame) using a three-headed gamma camera to assess the regional and total deposition and clearance of different radioaerosols over a period of 26 min. Six subjects inhaled nebulised technetium-99m diethylene triamine penta-acetic acid radiolabelled aerosols with small and large droplet sizes [mass median aerodynamic diameter (MMAD) 3.2 +/- 0.2 and 6.5 +/- 0.2 microm, span 1.8 and 1.7, respectively] and in normal (0.9%) or hypertonic (7%) saline with controlled breathing on four separate occasions. The penetration indices (PIs) calculated from the SPET data for normal saline were 0.50 +/- 0.04 and 0.36 +/- 0.02 for the small and large droplet sizes, respectively. Consistent with the hygroscopic growth of the hypertonic aerosols, the PIs for hypertonic saline were lower, at 0.43 +/- 0.02 and 0.34 +/- 0.02 for the small and large droplet sizes, respectively. PIs calculated from the planar data showed similar trends, but failed to detect the significant difference seen with SPET between small normal and small hypertonic saline radioaerosols. In conclusion, the feasibility of using fast dynamic SPET for imaging radioaerosol deposition and associated radiolabel clearance in the lung has been successfully demonstrated. The fast SPET was able to reveal important differences in aerosol deposition that were not detected by planar imaging.

Hyperosmotic shock induces both activation and translocation of glucose transporters in mammalian cells.

The effect of osmotic stress on sugar transport was investigated in Clone 9 epithelial cells, which express the glucose uniporter GLUT1, and in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4. An acute hyperosmotic shock increased the uptake of sugars in both cell types. In Clone 9 cells, this was followed by a regulatory volume increase (RVI) response. Stimulation of transport was rapid and reversible, with half-lives (t 1/2) for stimulation of 2-deoxy-D-glucose uptake of 5.6 +/- 0.9 (n=6) and 22.7 +/- 1.5 (n=4) min for Clone 9 cells and adipocytes respectively. The effect was dose dependent, reaching a maximum at 1.1 osM of 2.9 +/- 0.1-fold (n=3) for Clone 9 cells and 8.2 +/- 0.8-fold (n=3) for adipocytes. In the latter, this stimulation correlated with translocation of the glucose transporter isoform GLUT4 to the cell surface and was not significantly different from that elicited by 160 nM insulin (7.6 +/- 1.2-fold, n=3). The effect of osmotic shock was not, however, influenced by inhibitors of either phosphoinositide 3-kinase (PI 3-kinase) (wortmannin, 250 nM) or of p38 mitogen-activated protein kinase (p38 MAP kinase) (SB203580, 20 microM), which reportedly prevent GLUT4 translocation and/or activation by insulin respectively. These inhibitors also had no effect on the stimulation of transport by osmotic shock in Clone 9 cells. However, in contrast to adipocytes, the effect of osmotic shock on glucose transport in Clone 9 cells reflected primarily a change in the intrinsic activity of cell surface transporters and there was only a minor change in their subcellular distribution as assessed by cell immunostaining or no change as assessed by surface biotinylation. These results indicate that the response of cells to osmotic shock can involve changes both in transporter activity and location. The signal transduction pathways involved include neither PI 3-kinase nor the classical, osmotically-activated component, p38 MAP kinase.

Volume kinetics of intravenous fluid therapy in the prehospital setting.

INTRODUCTION: To study the volume effect of isotonic and hypertonic crystalloid fluid during ambulance transports after mild trauma, a prospective case-control study was initiated, using the ambulance and helicopter transport system in Stockholm. METHODS: The hemodilution resulting from intravenous infusion of 1.0 L of Ringer's acetate solution (n = 7) or 250 ml of 7.5% sodium chloride (n = 3) over 30 minutes (min) was measured every 10 min during 1 hour when fluid therapy was instituted at the scene of an accident, or on arrival at the hospital. The dilution was studied by volume kinetic analysis and compared to that of matched, healthy controls who received the same fluid in hospital. RESULT: The hemodilution at the end of the infusions averaged 7.7% in the trauma patients and 9.1% in the controls, but the dilution was better maintained after trauma. The kinetic analysis showed that the size of the body fluid space expanded by Ringer's solution was 4.6 L and 3.8 L for the trauma and the control patients, respectively, while hypertonic saline expanded a slightly larger space. For both fluids, trauma reduced the elimination rate constant by approximately 30%. CONCLUSION: Mild trauma prolonged the intravascular persistence of isotonic and hypertonic crystalloid fluid as compared to a control group.

A model of fluid and solute exchange in the human: validation and implications.

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Enhancement of sodium intestinal secretion in relation to absorption in malnourished rats. Hyperosmolar challenge.

Two experimental models were tried in young malnourished rats in order to study effect of an hyperosmolar challenge in the small intestine on the bi-directional fluxes of sodium. Weanling rats were fed with energy restricted diets. In model I 1 mL of NaCl 900 mOsm/kg was introduced in the small intestine of the rats and left from 5 up to 70 min, in order to determine the moment of higher net Na+ secretion, which occurred at 10 min. In model II, the bi-directional fluxes of Na+ and Cl- were studied using NaCl or mannitol 900 mOsm/kg under the effect of mecholil, atropine or 2-4 dinitrophenol, for 10 min. Mecholil decreased the Na+ absorption enhancing the net secretion. Control rats were used as reference. In the restricted diets animals occurred an increase of the net secretion stimulated by NaCl 900 mOsm/kg, and this effect was enhanced by mecholil. It is suggested that in malnutrition there is an impairment in Na- intestinal absorption.