Hypertonic/hyperoncotic solution in hypovolemic patients: experience in the emergency room

Hypertonic solutions have been studied extensively in the treatment of hypovolemic shock, both in experimental and clinical models. Safety, efficacy, and long-term effects on animals and patients have been evaluated. The present article reviews indications, safety, mortality rates, and outcome in patients with hemorrhagic hypovolemic shock who were treated after admission with a hypertonic/hyperoncotic solution under strict observation in the emergency room.

Effects of hypertonic sodium chloride solution on the electrophysiologic alterations caused by bupivacaine in the dog heart

The effects of various hypertonic solutions on the intraventricular conduction, ventricular repolarization and the arrhythmias caused by the intravenous (iv) injection of bupivacaine (6.5 mg/kg) were studied in sodium pentobarbital-anesthetized mongrel dogs. Hypertonic solutions, given iv 5 min before bupivacaine, were 7.5% (w/v) NaCl, 5.4% (w/v) LiCl, 50% (w/v) glucose (2,400 mOsm/l, 5 ml/kg), or 20% (w/v) mannitol (1,200 mOsm/l, 10 ml/kg). Bupivacaine induced severe arrhythmias and ventricular conduction and repolarization disturbances, as reflected by significant increases in QRS complex duration, HV interval, IV interval and monophasic action potential duration, as well as severe hemodynamic impairment. Significant prevention against ventricular electrophysiologic and hemodynamic disturbances and ventricular arrhythmias was observed with 7.5% NaCl (percent increase in QRS complex duration: 164.4 ± 21.8% in the non-pretreated group vs 74.7 ± 14.1% in the pretreated group, P<0.05; percent increase in HV interval: 131.4 ± 16.1% in the non-pretreated group vs 58.2 ± 7.5% in the pretreated group, P<0.05; percent increase in monophasic action potential duration: 22.7 ± 6.8% in the non-pretreated group vs 9.8 ± 6.3% in the pretreated group, P<0.05; percent decrease in cardiac index: -46 ± 6% in the non-pretreated group vs -28 ± 5% in the pretreated group, P<0.05). The other three hypertonic solutions were ineffective. These findings suggest an involvement of sodium ions in the mechanism of hypertonic protection.

Influence of different routes of flush perfusion on the distribution of lung preservation solutions in parenchyma and airways

Objective: The present study was performed to investigate the influence of different routes of perfusion on the distribution of the preservation solutions in the lung parenchyma and upper airways. Methods: Pigs were divided into four groups: control (n = 6), pulmonary artery (PA) (n = 6), simultaneous PA + bronchial artery (BA) (n = 8), and retrograde delivery (n = 6). After preparation and cannulation, cardioplegia solution and Euro- Collins solution (ECS) for lung preservation were given simultaneously. After removal of the heart, the double lung bloc was harvested. Following parameters were assessed: total and regional perfusion (dye-labeled microspheres), tissue water content, PA, aorta, left atrial and left ventricular pressures, cardiac output and lung temperature. Results: Our data show that flow of the ECS in lung parenchyma did not reach control values (9.4 ± 1.0 ml/min per g lung wet weight) regardless of the route of delivery (PA 6.3 ± 1.5, PA + BA 4.8 ± 0.9, retrograde 2.7 ± 0.9 ml/min per g lung wet weight). However, flow in the proximal and distal trachea were significantly increased by PA + BA delivery (0.970 ± 0.4, respectively, 0.380 ± 0.2 ml/min per g) in comparison with PA (0.023 ± 0.007, respectively, 0.024 ± 0.070 ml/min per g), retrograde (0.009 ± 0.003, respectively, 0.021 ± 0.006 ml/min per g) and control experiments (0.125 ± 0.0018, respectively, 0.105 ± 0.012 ml/g per min). Similarly the highest flow rates in the right main bronchus were achieved by PA + BA delivery (1.04 ± 0.4 ml/min per g) in comparison with 0.11 ± 0.03 in control, 0.033 ± 0.008 in PA, and 0.019 ± 0.005 ml/min per g in retrograde group. Flows in the left main bronchus were 0.09 ± 0.02 ml/min per g in control, 0.045 ± 0.012 ml/min per g in PA, and 0.027 ± 0.006 ml/min per g in retrograde group. The flow rates were significantly (P = 0.001) increased by PA + BA delivery of the storage solution (0.97 ± 0.3 ml/min per g). Conclusions: Our data show that the distribution of ECS for lung preservation is significantly improved in airway tissues (trachea and bronchi) if a simultaneous PA + BA delivery is used.

Comparison of the in vitro effects of saline, hypertonic hydroxyethyl starch, hypertonic saline, and two forms of hydroxyethyl starch on whole blood coagulation and platelet function in dogs.

OBJECTIVE To compare the in vitro effects of hypertonic solutions and colloids to saline on coagulation in dogs. DESIGN In vitro experimental study. SETTING Veterinary teaching hospital. ANIMALS Twenty-one adult dogs. INTERVENTIONS Blood samples were diluted with saline, 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH), 7.2% hypertonic saline (HTS), hydroxyethyl starch (HES) 130/0.4 or hydroxyethyl starch 600/0.75 at ratios of 1:22 and 1:9, and with saline and HES at a ratio of 1:3. MEASUREMENTS AND MAIN RESULTS Whole blood coagulation was analyzed using rotational thromboelastometry (extrinsic thromboelastometry-cloting time (ExTEM-CT), maximal clot firmness (MCF) and clot formation time (CFT) and fibrinogen function TEM-CT (FibTEM-CT) and MCF) and platelet function was analyzed using a platelet function analyzer (closure time, CTPFA ). All parameters measured were impaired by saline dilution. The CTPFA was prolonged by 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH) and HTS but not by HES solutions. At clinical dilutions equivalent to those generally administered for shock (saline 1:3, HES 1:9, and hypertonic solutions 1:22), CTPFA was more prolonged by HH and HTS than other solutions but more by saline than HES. No difference was found between the HES solutions or the hypertonic solutions. ExTEM-CFT and MCF were impaired by HH and HTS but only mildly by HES solutions. At clinically relevant dilutions, no difference was found in ExTEM-CFT between HTS and saline or in ExTEM-MCF between HH and saline. No consistent difference was found between the 2 HES solutions but HH impaired ExTEM-CFT and MCF more than HTS. At high dilutions, FibTEM-CT and -MCF and ExTEM-CT were impaired by HES. CONCLUSIONS Hypertonic solutions affect platelet function and whole blood coagulation to a greater extent than saline and HES. At clinically relevant dilutions, only CTPFA was markedly more affected by hypertonic solutions than by saline. At high dilutions, HES significantly affects coagulation but to no greater extent than saline at clinically relevant dilutions.

Flow-through peritoneal dialysis in neonatal enema-induced hyperphosphatemia

Fleet enemas are hypertonic solutions with an osmotic action and a high concentration of phosphate. When retained in the human body they have a great toxic potential, causing severe hydro-electrolyte disorders in children, especially in newborns. We report the case of a previously healthy 8-day-old newborn who needed neonatal intensive care treatment after the inadvertent administration of an osmotically active hypertonic phosphate enema. Taking into account that phosphate removal by peritoneal dialysis (PD) strongly depends on total dialysate turnover, we chose continuous flow PD (CFPD) as the treatment option, with a successful outcome. Clinical experience with this dialytic modality is limited to a few case reports in pediatric and adult patients. To the best of our knowledge, we report here the first description of CFPD in the setting of acute phosphate nephropathy in the neonatal period. The modality of PD described here has potential as an alternative management option as it is a highly efficient, methodologically simple, and low-cost method without any need for sophisticated equipment. Physicians and parents should be aware of the adverse effects of a hypertonic phosphate enema and should never use these medications in infants and newborns.

Soluciones hipertónicas en trauma craneoencefálico: revisión sistemática de la literatura

El traumatismo craneoencefálico, es la epidemia silenciosa de nuestra época, que genera gastos en salud, en países como Estados Unidos, cercanos a los 60 billones de dólares anuales, y cerca de 400 billones en rehabilitación de los discapacitados. El pilar del manejo médico del trauma craneoencefálico moderado o severo, es la osmoterapia, principalmente con sustancias como el manitol y las soluciones hipertónicas. Se realizó la revisión de 14 bases de datos, encontrando 4657754 artículos, quedando al final 40 artículos después de un análisis exhaustivo, que se relacionaban con el manejo de la hipertensión endocraneana y terapia osmótica. Resultados: Se compararon diferentes estudios, encontrando gran variabilidad estos, sin homogenización en los análisis estadísticos, y la poca rigurosidad no permitieron, la recolección de datos y la comparación entre los diferentes estudios, no permitió realizar el meta-análisis y por esto se decidió la realización de una revisión sistemática de la literatura. Se evidenció principalmente tres cosas: la primera es la poca rigurosidad con la que se realizan los estudios clínicos; la segunda, es que aún falta mucha más investigación principalmente, la presencia de estudios clínicos aleatorizados multicéntricos, que logren dar una sólida evidencia y que genere validez científica que se requiere, a pesar de la evidencia clara en la práctica clínica; la tercera es la seguridad para su uso, con poca presencia de complicaciones para las soluciones salinas hipertónicas.

G protein ss gamma subunits mediate presynaptic inhibition of transmitter release from rat superior cervical ganglion neurones in culture

The activation of presynaptic G protein-coupled receptors (GPCRs) is widely reported to inhibit transmitter release; however, the lack of accessibility of many presynaptic terminals has limited direct analysis of signalling mediators. We studied GPCR-mediated inhibition of fast cholinergic transmission between superior cervical ganglion neurones (SCGNs) in culture. The adrenoceptor agonist noradrenaline (NA) caused a dose-related reduction in evoked excitatory postsynaptic potentials (EPSPs). NA-induced EPSP decrease was accompanied by effects on the presynaptic action potential (AP), reducing AP duration and amplitude of the after-hyperpolarization (AHP), without affecting the pre- and postsynaptic membrane potential. All effects of NA were blocked by yohimbine and synaptic transmission was reduced by clonidine, consistent with an action at presynaptic alpha 2-adrenoceptors. NA-induced inhibition of transmission was sensitive to pre-incubation of SCGNs with pertussis toxin (PTX), implicating the involvement of G alpha(i)/(o)beta y subunits. Expression of G alpha transducin, an agent which sequesters G protein beta gamma (G beta y) subunits, in the presynaptic neurone caused a time-dependent attenuation of NA-induced inhibition. Injection of purified G beta gamma subunits into the presynaptic neurone inhibited transmission, and also reduced the AHP amplitude. Furthermore, NA-induced inhibition was occluded by pre-injection of G beta gamma subunits. The Ca2+ channel blocker Cd2+ mimicked NA effects on transmitter release. Cd2+, NA and G beta gamma subunits also inhibited somatic Ca2+ current. In contrast to effects on AP-evoked transmitter release, NA had no clear action on AP-independent EPSPs induced by hypertonic solutions. These results demonstrate that G beta gamma subunits functionally mediate inhibition of transmitter release by alpha 2-adrenoceptors and represent important regulators of synaptic transmission at mammalian presynaptic terminals.

Eficácia da solução de cloreto de sódio a 7,5% com e sem dextran 70 a 6% na preservação da função renal de cães hipovolêmicos submetidos à isquemia-reperfusão

JUSTIFICATIVA E OBJETIVOS: As soluções hipertônicas de cloreto de sódio, associadas ou não a colóides hiperoncóticos, podem ser eficazes em proteger o rim em situações de hipovolemia. O objetivo deste estudo foi verificar, em cães, o real benefício dessas soluções sobre a função renal, em vigência de hipovolemia e isquemia do órgão. MÉTODO: em 24 cães, anestesiados com pentobarbital sódico, submetidos à nefrectomia direita e à expansão volêmica com solução de Ringer (1 ml.kg-1.min-1), foram observadas possíveis alterações renais morfo-funcionais após hemorragia de 20 ml.kg-1 e trinta minutos de total isquemia renal esquerda, com posterior reperfusão, além da repercussão renal da administração de soluções de cloreto de sódio 7,5% (SH) e esta em dextran 70 a 6% (SHD). Atributos estudados: FC, PAM, pressão de veia cava inferior, fluxo sangüíneo renal, resistência vascular renal, hematócrito, Na+, K+, osmolaridade plasmática, PaO2, PaCO2 e pH, depuração (para-aminohipurato de sódio - PAH-1, creatinina, osmolar, água livre, Na+, K+), fração de filtração, volume e osmolaridade urinários, excreções urinárias e fracionárias de Na+ e K+ e exame histopatológico do rim. Os atributos foram estudados em três grupos (G1, G2 e G3) e em cinco momentos. RESULTADOS: Houve elevação estatisticamente significativa da pressão arterial média em G2 e G3, da resistência vascular renal em G1, do fluxo sangüíneo renal e da depuração de PAH em G3, da excreção fracionária de Na+ em G2 e G3, das depurações de creatinina, osmolar, de água livre e de Na+ e K+, da excreção urinária de Na+ e K+ e do volume urinário em G3. CONCLUSÕES: A SHD administrada 15 minutos após hemorragia moderada e 30 minutos antes de insulto isquêmico de 30 minutos foi eficiente em proteger o rim de cães das repercussões da isquemia-reperfusão. Não foi constatada alteração histopatológica renal à microscopia óptica.

Natriuresis induced by cholinergic stimulation of the locus coeruleus in the rat

Carbachol injected into the locus coeruleus (LC) induced a dose-dependent natriuresis in the rat. This natriuresis was maintained above control levels during the 120 min of urine sampling. Seizures and arterial blood pressure increase were also observed but they disappeared within 20 min after carbachol injection. Natriuresis was not obtained with either injections of carbachol outside the LC or with hypertonic solutions injected into the LC. Injection of atropine into the LC blocked the natriuresis induced by carbachol. In summary, our data show that carbachol induces natriuresis by an action on muscarinic receptors located in the LC region. © 1990.

Quali-quantitative study of the phenolic and polyphenolic compounds and their antioxidant capacity in vegetal matrix processed with different technologies

Food technologies today mean reducing agricultural food waste, improvement of food security, enhancement of food sensory properties, enlargement of food market and food economies. Food technologists must be high-skilled technicians with good scientific knowledge of food hygiene, food chemistry, industrial technologies and food engineering, sensory evaluation experience and analytical chemistry. Their role is to apply the modern vision of science in the field of human nutrition, rising up knowledge in food science. The present PhD project starts with the aim of studying and improving frozen fruits quality. Freezing process in very powerful in preserve initial raw material characteristics, but pre-treatment before the freezing process are necessary to improve quality, in particular to improve texture and enzymatic activity of frozen foods. Osmotic Dehydration (OD) and Vacuum Impregnation (VI), are useful techniques to modify fruits and vegetables composition and prepare them to freezing process. These techniques permit to introduce cryo-protective agent into the food matrices, without significant changes of the original structure, but cause a slight leaching of important intrinsic compounds. Phenolic and polyphenolic compounds for example in apples and nectarines treated with hypertonic solutions are slightly decreased, but the effect of concentration due to water removal driven out from the osmotic gradient, cause a final content of phenolic compounds similar to that of the raw material. In many experiment, a very important change in fruit composition regard the aroma profile. This occur in strawberries osmo-dehydrated under vacuum condition or under atmospheric pressure condition. The increment of some volatiles, probably due to fermentative metabolism induced by the osmotic stress of hypertonic treatment, induce a sensory profile modification of frozen fruits, that in some way result in a better acceptability of consumer, that prefer treated frozen fruits to untreated frozen fruits. Among different processes used, a very interesting result was obtained with the application of a osmotic pre-treatment driven out at refrigerated temperature for long time. The final quality of frozen strawberries was very high and a peculiar increment of phenolic profile was detected. This interesting phenomenon was probably due to induction of phenolic biological synthesis (for example as reaction to osmotic stress), or to hydrolysis of polymeric phenolic compounds. Aside this investigation in the cryo-stabilization and dehydrofreezing of fruits, deeper investigation in VI techniques were carried out, as studies of changes in vacuum impregnated prickly pear texture, and in use of VI and ultrasound (US) in aroma enrichment of fruit pieces. Moreover, to develop sensory evaluation tools and analytical chemistry determination (of volatiles and phenolic compounds), some researches were bring off and published in these fields. Specifically dealing with off-flavour development during storage of boiled potato, and capillary zonal electrophoresis (CZE) and high performance liquid chromatography (HPLC) determination of phenolic compounds.

Fluid Replacement With Hypertonic or Isotonic Solutions Guided by Mixed Venous Oxygen Saturation in Experimental Hypodynamic Sepsis

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoneotic solution Would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 Minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

Antagonism produced by hypertonic nutrient solutions on the depressive effect of carbofuran on isolated guinea pig atria

The action of hyperosmotic nutrient solutions on the depressive effects of carbofuran was studied on spontaneously contracting guinea pig atria. The force and frequency of contraction were recorded using an isotonic lever. Carbofuran 33.0 mu g ml(-1) produced a gradual depressive effect. The time for stabilization of the depressive effect was 6.0+/-2.3 min. After the depressive effect of carbofuran was established, NaCI, mannitol, or urea were introduced into the organ bath to increase the osmolarity of the nutrient solution to about 100 mosmol kg(-1) of water. This resulted in a reversal of the contraction force and frequency to the initial levels. The addition of the osmotic agents at the same concentrations before the addition of 33.0 mu g ml(-1) carbofuran avoided its depressive effect on guinea pig atria. (C) 1996 the Italian Pharmacological Society.

The release of antidiuretic hormone is appropriate in response to hypovolemia and/or sodium administration in children with severe head injury: a trial of lactated Ringer's solution versus hypertonic saline.

We conducted an open, randomized, and prospective study to determine the effect of hypertonic saline on the secretion of antidiuretic hormone (ADH) and aldosterone in children with severe head injury (Glasgow coma scale <8). Thirty-one consecutive patients at a level III pediatric intensive care unit at a children's hospital received either lactated Ringer's solution (Ringer's group, n = 16) or hypertonic saline (Hypertonic Saline group, n = 15) over a 3-day period. Serum ADH levels were significantly larger in the Hypertonic Saline group as compared with the Ringer's group (P = 0.001; analysis of variance) and were correlated to sodium intake (Ringer's group: r = 0.39, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.42, R(2) = 0.18, P = 0.02) and volume of fluids given IV (Ringer's group: r = 0.38, R(2) = 0.15, P = 0.02; Hypertonic Saline group: r = 0.32, R(2) = 0.1, P = not significant). Correlation of ADH to plasma osmolality was significant if plasma osmolality was >280 mOsm/kg (r = 0.5, R(2) = 0.25, P = 0.06), indicating an osmotic threshold for ADH release. Serum aldosterone levels were larger on the first day than during Days 2 and 3 in both groups and inversely correlated to serum sodium levels only in the Ringer's group (r = -0.55, R(2) = 0.3, P < 0.001). This group received a significantly larger fluid volume on Day 1 (P = 0.05, Mann-Whitney U-test) than did patients in the Hypertonic Saline group, indicating hypovolemia during the first day. Head-injured children have appropriate levels of ADH. They may be hypovolemic during the first day of treatment, especially if they receive lactated Ringer's solution. IMPLICATIONS: In head-injured patients, we recommend fluid restriction to avoid inappropriate secretion of antidiuretic hormone. In a prospective, randomized, and controlled study in 31 children, we were able to show that the antidiuretic hormone levels are appropriate in response to hypovolemia, sodium load, or both.

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.