Hypertonic Saline Group Research Articles

Cerebral Hemodynamic and Metabolic Effects of Equi-Osmolar Doses Mannitol and 23.4% Saline in Patients with Edema Following Large Ischemic Stroke

Cerebral edema after ischemic stroke is frequently treated with mannitol and hypertonic saline (HS); however, their relative cerebrovascular and metabolic effects are incompletely understood, and may operate independent of their ability to lower intracranial pressure. We compared the effects of 20% mannitol and 23.4% saline on cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and oxygen metabolism (CMRO(2)), in nine ischemic stroke patients who deteriorated and had >2 mm midline shift on imaging. (15)O-PET was performed before and 1 h after administration of randomly assigned equi-osmolar doses of mannitol (1.0 g/kg) or 23.4% saline (0.686 mL/kg). Baseline CBF values (ml/100g/min) in the infarct core, periinfarct region, remaining ipsilateral hemisphere, and contralateral hemisphere in the mannitol group were 5.0 ± 3.9, 25.6 ± 4.4, 35.6 ± 8.6, and 45.5 ± 2.2, respectively, and in the HS group were 8.3 ± 9.8, 35.3 ± 10.9, 38.2 ± 15.1, and 35.2 ± 12.4, respectively. There was a trend for CBF to rise in the contralateral hemisphere after mannitol from 45.5 ± 12.2 to 57.6 ± 21.7, P = 0.098, but not HS. CBV, OEF, and CMRO(2) did not change after administration of either agent. Change in CBF in the contralateral hemisphere after osmotic therapy was strongly correlated with baseline blood pressure (R (2)= 0.879, P = 0.002). We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue. We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue.

Effect of inhaled hypertonic saline on hospital admission rate in children with viral bronchiolitis: a randomized trial

We sought to determine whether inhaled 3% hypertonic saline (HS) reduces admission to hospital in ambulatory children with moderately severe viral bronchiolitis. Secondary objectives compared changes in respiratory scores before and after treatment and assessed the need for unscheduled medical intervention within 7 days. Children under the age of 2 years presenting with moderately severe viral bronchiolitis to the emergency department of 4 general hospitals from November 2008 to March 2009 were randomly assigned to receive 3 consecutive 4-mL doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group) in a double blind fashion, each coadministered with 1 mg salbutamol. Outcome measures included the difference in hospital admission rate and changes in respiratory distress scores. A total of 81 children (mean age 8.9 mo, range 0.7-22 mo) were assessed over 88 visits on an intention-to-treat basis. No statistically significant differences were found between treatment groups. Children in the HS group had a nonsignificant trend toward greater improvement compared with NS controls with a same-day admission rate of 18% (95% confidence interval [CI] 9%-32%) versus 27% (95% CI 16%-42%), respectively. Respiratory Assessment Change Scores (RACS) favoured the HS group over NS controls (mean RACS 4.7 [95% CI 3.6-5.8] v. 3.7 [95% CI 2.5-4.9], respectively), although the CIs overlap and these differences were not statistically significant. The short-term use of nebulized 3% HS did not result in any statistically significant benefits, although a nonsignificant trend toward a decrease in admission rate and improvement in respiratory distress was found. A larger study would be required to determine whether these trends arise from a clinically relevant treatment effect.

Efeitos cardiovascular e metabólico da reposição volêmica com solução salina hipertônica 7,5% associada ou não ao hidroxietilamido 130/0,4 em gatas com hipovolemia induzida

A hipovolemia é caracterizada por uma perda de fluido corpóreo, cursando com inadequado fluxo circulatório e consequentemente lesão tecidual. Neste trabalho, objetivou-se comparar a expansão volêmica resultante da administração de solução salina hipertônica (NaCl 7,5%), isolada ou em associação com hidroxietilamido 130/0,4 (HES 130/0,4), em gatas com hipovolemia induzida, sob anestesia geral inalatória com isofluorano. Foram utilizadas 12 gatas, sem raça definida, adultas, com massa corporal média de 3,07±0,56kg. Os animais foram anestesiados com isofluorano e, após a preparação cirúrgica, foram mantidos em 1CAM sob ventilação controlada. Após a estabilização do plano anestésico, foram avaliados os parâmetros basais. Em ato contínuo, iniciou-se a fase de hipovolemia, por meio da retirada de 30ml kg-1 de sangue da artéria femoral. Após 60 minutos da estabilização do quadro de hipovolemia, foi realizada nova mensuração dos dados, alocando-se os animais aleatoriamente em dois grupos: GSH (grupo solução hipertônica, n=6), que receberam, na fase de expansão volêmica, NaCl 7,5% isolada, na dose de 4ml kg-1, e GSHC (grupo salina hipertônica associado ao coloide, n=6), que receberam NaCl 7,5%, na mesma dose citada, em associação com HES 130/0,4, na dose de 30ml kg-1. Após realização do tratamento, foram avaliados novamente os efeitos cardiovasculares e hemogasométricos por 120 minutos. As pressões arteriais média (PAM), sistólica (PAS) e diastólica (PAD) foram maiores logo após a expansão volêmica (T0) para o GSH. De T45 até T120, as PAM, PAS e PAD foram maiores para o GSHC, em comparação com o GSH. A pressão venosa central foi maior no GSHC até T60. Não foram observadas diferenças entre grupos para frequência cardíaca e respiratória, íons sódio e potássio, déficit de base, bicarbonato, saturação de oxigênio na hemoglobina, glicose, PaCO2, PaO2 e pH. Conclui-se que a administração de NaCl 7,5% isoladamente aumenta rapidamente a PAM, PAS e PAD em gatos com hipovolemia induzida, mantendo esse efeito por apenas 30 minutos, enquanto que a administração de hidroxietilamido 130/0,4 associado à NaCl 7,5% promove reestabelecimento mais tardio (após 30 minutos), porém mais duradouro (até 120 minutos) da PAM, PAS e PAD em gatas com hipovolemia induzida. A administração de HES 130/0,4 associada à NaCl 7,5% promove aumento acentuado da PVC por até 60 minutos após a administração.

Clinical Experience Using 5% Hypertonic Saline as a Safe Alternative Fluid for Use in Trauma

Published experience of hypertonic saline (HTS) use in resuscitation has described the use of commercially unavailable 7.5% solutions. The purpose of this study was to compare our experience with the administration of commercially available 5% HTS solution with that of well-matched controls who did not receive HTS. Prospective observational study of 51 trauma patients receiving 500 mL of 5% HTS during initial resuscitation. Patients who received HTS were 1:2 matched using age, gender, Injury Severity Score, Coma Score, Head Abbreviated Injury Scale, and injury mechanism to trauma patients who did not receive HTS. The laboratory values and outcomes of the two groups were compared. Patients receiving HTS demonstrated no difference from the matched cohort in mean pH, international normalized ratio, or p/f ratios at 8 hours or 24 hours. The mean serum sodium of the HTS group was higher than controls at 8 hours (143.1 vs. 150.1 mg/dL, p < 0.001) and remained significantly more increased for 3 days without any adverse sequelae related to hypernatremia. No difference in mortality was noted between the two groups. A trend in decreased mortality was observed in patients with Coma Score <or=8 and Head Abbreviated Injury Scale score >or=3 (25.0% vs. 42.5%). The mean ventilator days were 7.3 for HTS group and 9.2 for the non-HTS group. Although serum sodium remained increased for several days after HTS administration, no adverse sequelae as a result of hypernatremia resulted. Commercially available 5% HTS solution is safe for use in the resuscitation of trauma patients and may improve outcomes in a selected subset of patients with head injury.

A Comparison of 3% Hypertonic Saline and Mannitol for Brain Relaxation During Elective Supratentorial Brain Tumor Surgery

In this study, we compared the effects of 3% hypertonic saline (HTS) and 20% mannitol on brain relaxation during supratentorial brain tumor surgery, intensive care unit (ICU) stays, and hospital days. This prospective, randomized, and double-blind study included patients who were selected for elective craniotomy for supratentorial brain tumors. Patients received either 160 mL of 3% HTS (HTS group, n = 122) or 150 mL of 20% mannitol infusion (M group, n = 116) for 5 minutes at the start of scalp incision. The PCO(2) in arterial blood was maintained within 35 to 40 mm Hg, arterial blood pressure was controlled within baseline values +/-20%, and positive fluid balance was maintained intraoperatively at a rate of 2 mL/kg/h. Outcome measures included fluid input, urine output, arterial blood gases, serum sodium concentration, ICU stays, and hospital days. Surgeons assessed the condition of the brain as "tight," "adequate," or "soft" immediately after opening the dura. Brain relaxation conditions in the HTS group (soft/adequate/tight, n = 58/43/21) were better than those observed in the M group (soft/adequate/tight, n = 39/42/35; P = 0.02). The levels of serum sodium were higher in the HTS group compared with the M group over time (P < 0.001). The average urine output in the M group (707 mL) was higher than it was in the HTS group (596 mL) (P < 0.001). There were no significant differences in fluid input, ICU stays, and hospital days between the 2 groups. Our results suggest that HTS provided better brain relaxation than did mannitol during elective supratentorial brain tumor surgery, whereas it did not affect ICU stays or hospital days.

Bronchiolitis in ED: Nebulized Hypertonic Saline/Epinephrine?

Source: Grewal S, Ali S, McConnell DW, et al. A randomized trial of nebulized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department. Arch Pediatr Adolesc Med. 2009; 163:(11) 1007– 1012; doi: 10.1001/archpediatrics.2009.196To determine whether nebulized 3% hypertonic saline has a clinical benefit in infants with bronchiolitis, a randomized, double-blind, controlled trial was performed in the emergency department (ED) on 46 infants with mild to moderate bronchiolitis. All patients were selected from the pediatric ED at Stollery Children’s Hospital in Edmonton, Alberta, Canada. Infants aged 6 weeks to 12 months seen with a first episode of wheezing, clinical symptoms of a viral respiratory infection, an initial oxygen saturation of 85%–96%, and an initial Respiratory Distress Assessment Instrument (RDAI) score of 4 or higher were included in the study. The RDAI score ranges from 0 to 17 and is calculated based on wheezing type and location and retraction severity and location. Exclusion criteria included pre-existing cardiac or pulmonary disease, previous diagnosis of asthma by a physician, any use of bronchodilators prior to the current illness, language barrier, and no telephone access for follow-up.The selected infants were randomly assigned to receive either hypertonic saline containing 2.5 mL of 3% saline with 0.5 mL of 2.25% racemic epinephrine, or the same volume of normal saline (0.9% saline) with 2.25% racemic epinephrine. All were administered via a nebulizer driven by a 6 L/min flow of oxygen. A repeat dose could be given at the discretion of the ED physician. Measurements of oxygen saturation, respiratory rate, heart rate, and RDAI score were made immediately prior to administration of the aerosol, and at 30, 60, 90, and 120 minutes after administration. One patient in each group withdrew or was dropped. Baseline characteristics of the two groups were similar with regard to age, gender, family history of asthma, smoke exposure, respiratory syncytial virus positivity (82.6% and 81.8%, respectively, for the hypertonic saline and normal saline groups), and baseline respiratory rate.A discretionary second dose was administered in 56% (13/23) of the hypertonic saline group and 48% (11/23) of the normal saline (control) group. No differences between the two groups in respiratory distress, oxygen saturation, or returns to the ED (3/23 vs 4/23) were apparent. Additionally, while a difference with regard to hospital admission was noted between the hypertonic saline group (8/23) and the normal saline group (13/23), this difference did not reach statistical significance.The authors conclude that 3% hypertonic saline did not demonstrate the effectiveness in this ED setting that had been demonstrated in inpatient studies.While this study was unable to identify a significant benefit from one or two doses of 3% hypertonic saline during a two-hour period, the results differ from those of an ambulatory study of infants with bronchiolitis seen at the Pediatric and Adolescent Ambulatory Community Clinic of General Health Services of Petach-Tikva, Israel,1 which found a significant decrease in symptoms during the first two days from three-times-daily use, a result similar to that seen in three inpatient studies included in a Cochrane review.2 While there was no decrease in the rate of hospitalization in that study, it was low (6%–9%) in both groups. The current study found fewer hospitalizations in the 3% hypertonic saline group. While the differences in hospitalization were not statistically significant, the possibility of a type 2 error (accepting the absence of a population difference based on a relatively small sample) must be considered.The data available from the various studies now support routine use of 3% hypertonic saline with either epinephrine or a β2 agonist such as albuterol in hospitalized patients with the expectation of more rapid clinical improvement and a one-day decrease in hospital stay. Use in the ED is not yet routinely justified, but a larger study powered to examine further the potential for decreasing hospitalizations would be needed. For infants not requiring hospitalization, more rapid improvement in symptoms from hypertonic saline must be weighed against the expense and inconvenience of three-times-daily use of an aerosol for a self-limited problem with a low likelihood of requiring repeat emergent care or hospitalization. Although not yet studied, it would be of interest to see if there is any benefit to using hypertonic saline in more severe bronchiolitis patients at risk for or requiring assisted ventilation.

The role of pre-hospital blood gas analysis in trauma resuscitation

BackgroundTo assess, whether arterial blood gas measurements during trauma patient's pre-hospital shock resuscitation yield useful information on haemodynamic response to fluid resuscitation by comparing haemodynamic and blood gas variables in patients undergoing two different fluid resuscitation regimens.MethodsIn a prospective randomised study of 37 trauma patients at risk for severe hypovolaemia, arterial blood gas values were analyzed at the accident site and on admission to hospital. Patients were randomised to receive either conventional fluid therapy or 300 ml of hypertonic saline. The groups were compared for demographic, injury severity, physiological and outcome variables.Results37 patients were included. Mean (SD) Revised Trauma Score (RTS) was 7.3427 (0.98) and Injury Severity Score (ISS) 15.1 (11.7). Seventeen (46%) patients received hypertonic fluid resuscitation and 20 (54%) received conventional fluid therapy, with no significant differences between the groups concerning demographic data or outcome. Base excess (BE) values decreased significantly more within the hypertonic saline (HS) group compared to the conventional fluid therapy group (mean BE difference -2.1 mmol/l vs. -0.5 mmol/l, p = 0.003). The pH values on admission were significantly lower within the HS group (mean 7.31 vs. 7.40, p = 0.000). Haemoglobin levels were in both groups lower on admission compared with accident site. Lactate levels on admission did not differ significantly between the groups.ConclusionPre-hospital use of small-volume resuscitation led to significantly greater decrease of BE and pH values. A portable blood gas analyzer was found to be a useful tool in pre-hospital monitoring for trauma resuscitation.

Hypertonic saline reduces metalloproteinase expression in liver during pancreatitis

1. We recently demonstrated that hypertonic saline reduces inflammation and mortality in acute pancreatitis. The present study investigated the effects of hypertonic saline in metalloproteinase (MMP) regulation and pancreatitis-associated hepatic injury. 2. Wistar rats were divided into four groups: (i) control, not subjected to insult or treatment; (ii) no treatment (NT), induction of pancreatitis (retrograde infusion of 2.5% sodium taurocholate (1.0 mL/kg)), but no further treatment; (iii) normal saline (NS), induction of pancreatitis and treatment with normal saline (0.9% NaCl, 34 mL/kg, i.v. bolus, 1 h after the induction of pancreatitis); and (iv) hypertonic saline (HS), induction of pancreatitis and treatment with hypertonic saline (7.5% NaCl, 4 mL/kg administered over a period of 5 min, 1 h after the induction of pancreatitis). In all four groups, 4, 12 and 24 h after the induction of pancreatitis, liver tissue samples were assayed to determine levels of MMP-2, MMP-9, 47 kDa heat shock protein (HSP47) and collagen (Type I and III). 3. Compared with the control group, MMP-9 expression and activity was increased twofold in the NS and NT groups 4 and 12 h after the induction of pancreatitis, but remained at basal levels in the HS group. In contrast, MMP-2 expression was increased twofold 12 h after the induction of pancreatitis only in the NS group, whereas the expression of HSP47 was increased 4 h after the induction of pancreatitis in the NS and NT groups. Greater extracellular matrix remodelling occurred in the NS and NT groups compared with the HS group, probably as a result of the hepatic wound-healing response to repeated injury. However, the collagen content in hepatic tissue remained at basal levels in the HS group. 4. In conclusion, the results of the present study indicate that hypertonic saline is hepatoprotective and reduces hepatic remodelling, maintaining the integrity of the hepatic extracellular matrix during pancreatitis. Hypertonic saline-mediated regulation of MMP expression may have clinical relevance in pancreatitis-associated liver injury.

Effects of Different Resuscitation Fluids on Acute Lung Injury in a Rat Model of Uncontrolled Hemorrhagic Shock and Infection

To investigate the effects of different resuscitation fluids on acute lung injury in a rat model of uncontrolled hemorrhagic shock (HS) followed by mimicked infection. Sixty Sprague-Dawley rats were randomly assigned to one of the five groups (n = 12 per group) to receive the following treatments: (1) control group (group C), surgery, no hemorrhage, and no resuscitation; (2) no fluid resuscitation group; (3) lactated Ringer's solution group; (4) 7.5% hypertonic saline (HTS) group; and (5) hydroxyethyl starch group (group HES). All experimental groups were subjected to three phases: phase I entailed massive hemorrhage with a mean arterial pressure of 35 mm Hg to 40 mm Hg for 60 minutes by tail amputation and followed by mimicked infection by intratracheal administration of lipopolysaccharide 2 mg/kg. The animals in each group were then partially resuscitated with the fluid assigned to the group. Phase II of 60 minutes commenced at tail ligation, involved hemostasis, and return of all the blood initially shed. Phase III was an observation phase with no any further treatment and lasted for 3.5 hours. The survival rate at the end of the phase III was recorded. After phase III, arterial blood gases were recorded. The wet to dry lung weight ratio, pulmonary microvascular permeability, the expression of transforming growth factor (TGF)-beta1, and Smad2 were determined. The lung histology was also assessed. HES and HTS solutions were more effective than no fluid resuscitation and lactated Ringer's solution in reducing the detrimental effects of HS and infection on the lungs, as seen by the significantly lower pulmonary microvascular permeability and wet to dry lung weight ratio, the improved arterial blood gases and lower levels of TGF-beta1and Smad2 expression in lung tissues. These beneficial effects were most pronounced in the group HES. This study demonstrated that resuscitation with HTS and especially with HES could reduce lung tissue damage and pulmonary edema after severe uncontrolled HS. The TGF-beta1/Smad2 signaling pathway might play a key role in regulation of pulmonary permeability and formation of pulmonary edema in a rat model of uncontrolled HS and infection.

A Randomized Trial of Nebulized 3% Hypertonic Saline With Epinephrine in the Treatment of Acute Bronchiolitis in the Emergency Department

To determine whether nebulized 3% hypertonic saline with epinephrine is more effective than nebulized 0.9% saline with epinephrine in the treatment of bronchiolitis in the emergency department. Randomized, double-blind, controlled trial. Single-center urban pediatric emergency department. Infants younger than 12 months with mild to moderate bronchiolitis. Patients were randomized to receive nebulized racemic epinephrine in either hypertonic or normal saline. The primary outcome measure was the change in respiratory distress, as measured by the Respiratory Assessment Change Score (RACS) from baseline to 120 minutes. The change in oxygen saturation was also determined. Secondary outcome measures included the rates of hospital admission and return to the emergency department. Forty-six patients were enrolled and evaluated. The 2 study groups had similar baseline characteristics. The RACS from baseline to 120 minutes demonstrated no improvement in respiratory distress in the hypertonic saline group compared with the normal saline control group. The change in oxygen saturation in the hypertonic saline group was not significant when compared with the control group. Rates of admission and return to the emergency department were not different between the 2 groups. In the treatment of acute bronchiolitis, hypertonic saline and epinephrine did not improve clinical outcome any more than normal saline and epinephrine in the emergency setting. This differs from previously published results of outpatient and inpatient populations and merits further evaluation. isrctn.org Identifier: ISRCTN66632312.

Donor Pretreatment With Hypertonic Saline Attenuates Primary Allograft Dysfunction

Hypertonic saline (HTS) has been previously demonstrated to have immune modulatory and vascular protective effects. We assessed the effect of donor pretreatment with HTS on allograft preservation in a porcine model of orthotopic heart transplantation. Orthotopic transplants were performed after 6 hours of cold static allograft storage. Donor pigs were randomly assigned to pretreatment with (n=7) or without (n=6) HTS (4.5 mL/kg of 7.5% NaCl) administered 1 hour before donor heart arrest. Administration of HTS increased serum sodium level from 138+/-2 mmol/L to 154+/-4 mmol/L, which normalized to 144+/-3 mmol/L 1 hour after infusion. Successful weaning from cardiopulmonary bypass was significantly greater in HTS-treated hearts (6/7 vs 1/6; P=0.029). Preload recruitable stroke work after transplantation was improved compared to control (88+/-21% vs 35+/-8% of baseline; P=0.0001). Similarly, end-systolic elastance was improved compared to control (85+/-17% vs 42+/-12% of baseline; P=0.0002). Posttransplantation systolic blood pressure was significantly higher in the donor HTS group (60+/-9 mm Hg vs 35+/-6 mm Hg; P=0.04). Donor HTS treatment improved coronary artery endothelial-dependent vasorelaxation compared with control (Emax: HTS, 59+/-4%; control, 47+/-3%; P=0.04). HTS also resulted in improved endothelial-independent vasorelaxation compared with control (Emax: HTS, 71+/-3%; control, 59+/-4%; P=0.03; ED-50: HTS, 0.56x10 to 6+/-0.23 mol/L; control, 2.5x10 to 6+/-1.0 mol/L; P=0.04). Sensitivity to endothelin-1-induced vasospasm was reduced with HTS pretreatment (% maximum contraction [Cmax]: HTS, 338+/-15%; control, 419+/-40%; P=0.01). Donor HTS pretreatment attenuates posttransplantation cardiac allograft myocardial dysfunction, improves posttransplantation systemic hemodynamic function, and preserves posttransplantation cardiac allograft vascular function. HTS may be a novel organ donor intervention to prevent primary graft dysfunction.

Small volume resuscitation with 3% hypertonic saline solution decrease inflammatory response and attenuates end organ damage after controlled hemorrhagic shock

Background Recently, studies have been conducted examining the efficacy of 3% hypertonic saline solution (HS) for the treatment of traumatic brain injury; however, few studies have analyzed the effects of 3% hemorrhagic shock during hemorrhagic shock. The aim of this study was to test the potential immunomodulatory benefits of 3% hemorrhagic shock resuscitation over standard fluid resuscitation. Methods Wistar rats were bled to a mean arterial pressure of 35 mm Hg and then randomized into 3 groups: those treated with lactated Ringer's solution (LR; 33 mL/kg, n = 7), 3% HS (10 mL/kg, n = 7), and 7.5% HS (4 mL/kg, n = 7). Half of the extracted blood was reinfused after fluid resuscitation. Animals that did not undergo shock served as controls (n = 5). Four hours after hemorrhagic shock, blood was collected for the evaluation of tumor necrosis factor–α and interleukin-6 by enzyme immunoassay. Lung and intestinal samples were obtained for histopathologic analysis. Results Animals in the HS groups had significantly higher mean arterial pressure than those in the LR group 1 hour after treatment. Osmolarity and sodium levels were markedly elevated in the HS groups. Tumor necrosis factor–α and interleukin-6 levels were similar between the control and HS groups but significantly higher in the LR group ( P < .05). The lung injury score was significantly higher in the LR group compared with the 7.5% HS and 3% HS groups (5.7 ± 0.7, 2.1 ± 0.4, and 2.7 ± 0.5, respectively). Intestinal injury was attenuated in the 7.5% HS and 3% HS groups compared with the LR group (2.0 ± 0.6, 2.3 ± 0.4, and 5.9 ± 0.6, respectively). Conclusions A small-volume resuscitation strategy modulates the inflammatory response and decreases end-organ damage after HS. Three percent HS provides immunomodulatory and metabolic effects similar to those observed with conventional concentrations of HS.

Hyper osmolality does not modulate natriuretic peptide concentration in patients after coronary artery surgery

The heart secretes natriuretic peptides (NPs) in response to myocardial stretch. Measuring NP concentrations is a helpful tool in guiding treatment. It has been suggested that sodium ion and hyperosmolality could affect NP excretion. If this is true, peri-operative NP measurements could be inconsistent when hypertonic solutions are used. With different osmolalities but equal volumes of hydroxyethyl starch (HES)--and hypertonic saline (HS)--infusions, this double-blinded study tested the hypothesis that osmolality modulates the excretion of NPs. Fifty coronary surgery patients were randomized to receive within 30 min 4 ml/kg either HS or HES post-operatively. Samples for analysis of atrial NP (ANP), brain NP (BNP), plasma and urine sodium and osmolality and urine oxygen tension were obtained before and 60 min after starting the infusions and on the first post-operative morning. The haemodynamic parameters were measured at the same time points. Plasma osmolality and sodium increased only in the HS group. Changes in plasma BNP and ANP levels did not differ between the groups (P=0.212 and 0.356). There were no correlations between NP levels and osmolality or sodium at any time point. In the HS group, urine volume was higher (3295 vs. 2644 ml; P<0.05) and the need for furosemide treatment was less (0.4 vs. 3.8 mg; P<0.01) than in the HES group. The absence of effects of plasma sodium content or hyperosmolality on NP release validates the value of NPs as a biomarker in peri-operative patients.

Hypertonic stimulation induces synthesis and release of glutamate in cultured rat hypothalamic astrocytes and C6 cells

To investigate whether hypertonic saline (HS) can induce the synthesis and release of glutamate in cultured hypothalamic astrocytes or C6 cell line. Astrocytes were isolated, cultured, purified and identified from the hypothalamus of newborn rat (1 day). The astrocytes were randomly divided into five groups: isotonic (IS) and HS groups, astrocytes were incubated by IS and HS (320 mosM NaCl) medium, respectively, for 1, 3, 5, 10 or 15 min; carbenoxolone (CBX)+IS and CBX+HS groups, astrocytes were pre-treated with CBX (100 mmol/L) for 1 h at 37 degrees C in a 5% CO(2) / 95% atmosphere, then removed to IS and HS medium, respectively, for 1, 3, 5, 10 or 15 min; Ca(2+)+HS group, astrocytes were pre-incubated with Ca Ca(2+) (1,000 micromol/L) for 1 h at 37 degrees C in a 5% CO(2) / 95% atmosphere, followed by a wash with isotonic FBS/DMEM, and then removed to hypertonic saline for 1, 3, 5, 10 or 15 min. The media of five groups were collected to analyze the medium glutamate concentration with high performance liquid chromatography. The astrocytes were fixed and double immunofluorescent stained with anti-glial fibrillary acidic protein (GFAP) and anti-glutamate. The C6 cells were divided into four groups: IS, HS, CBX+IS and CBX+HS groups, and used for quantitative measurement of glutamate in cells by flow cytometry (FCM). (1) Anti-GFAP immunofluorescent signal revealed no significant difference among various time points in each group, or among the five groups. (2) The anti-glutamate immunofluorescent signal was increased in HS group and peaked at 5 min, and decreased and returned to the level of IS group at 15 min (P < 0.01 vs the 5 min of HS group). In CBX+HS group, the glutamate intensity was higher than that in CBX+IS and HS groups. (3) The medium glutamate concentration had no change after treatment with HS for 1 and 3 min, while increased markedly after treatment for 5 min to 15 min (P< 0.01 vs 1 min and 3 min). On the contrary, the medium glutamate concentrations in the CBX+HS or Ca(2+)+HS group were significant lower than that in the HS group (P < 0.01). (4) FCM showed HS and CBX+HS induced glutamate increase in C6 cells. HS induced cultured rat hypothalamic astrocytes or C6 cells to synthesize and release glutamate; CBX could block glutamate release, but could not disrupt glutamate synthesis.

Abstract 2329: Donor Pretreatment with Hypertonic Saline Attenuates Primary Cardiac Allograft Dysfunction

Objective: Hypertonic saline (HTS) has been previously demonstrated to have immune modulatory and vascular protective effects. We assessed the effect of donor pretreatment with HTS on allograft myocardial function in a porcine model of orthotopic heart transplantation. We hypothesized that HTS infusion prior to donor heart arrest and storage would limit ischemia-reperfusion injury and improve myocardial performance following transplantation. Methods: Orthotopic transplants were performed after 6 hours of ischemic allograft storage. Donor pigs were randomly assigned to pretreatment with (n = 7) or without (n = 6) HTS (4.5 ml/kg of 7.5% NaCl) administered 1 hour prior to donor heart arrest. Left ventricular performance was determined after caval occlusion using a Millar micromanometer and conductance catheter. Hemodynamic measurements were obtained using a Swan-Ganz catheter. Results: Administration of hypertonic saline increased serum sodium level from 138 ± 2 mmol/L to 154 ± 4 mmol/L, which normalized to 144 ± 3 mmol/L 1 hour post-infusion. Weaning from CPB and LV performance after transplantation was improved after donor HTS treatment. Successful weaning from CPB was significantly greater in HTS treated hearts (6/7 versus 1/6, p &lt; 0.05). Preload recruitable stroke work post-transplantation was improved compared to control (88 ± 21% versus 35 ± 8% of baseline, p &lt; 0.01). Similarly, maximal elastance was improved compared to control (85 ± 17% versus 42 ± 12% of baseline, p = 0.03). No significant differences in post-transplant central venous, pulmonary artery or pulmonary capillary wedge pressures were observed between groups. However, post-transplant systolic blood pressure was significantly higher in the donor HTS group (60 ± 9 mmHg versus 35 ± 6 mmHg, p = 0.04). Conculsions: Donor HTS pretreatment attenuates post-transplant cardiac allograft myocardial function and improves post-transplant systemic hemodynamic function. HTS may be a novel organ donor intervention to prevent primary graft dysfunction. Further clinical evaluation of this simple and potentially cost-effective intervention is warranted.

Effect of HSH on oxygen free radicals and histopathological change of brain tissue in dog with acute intracranial hypertension and hemorrhagic shock

Objective To observe the effects of hypertonic sodium chloride hydroxyethyl starch 40 injection(HSH) on recovering of circulating blood volume, lessening edema of brain tissue and decreasing oxygen free radicals in dog with acute intracranial hypertension and hemorrhagic shock. Methods 20 healthy dogs were randomly divided into 4 groups: Group hydroxyethyl starch (HES), Group Ringer- lactate solution (RL), Group hypertonic saline solution (HS) and Group HSH. Acute intracranial hypertension and hemorrhagic shock were made by injecting water into epidural balloon and bleeding artery. Corresponding injections were infused respectively 1h after shock. Mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR) and intracranial pressure (ICP) were monitored, and the level of superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue were examined. Specimens of brain tissue were prepared for pathological examination. Results After resuscitation, injections of 4 groups can effectively increase MAP( P < 0.05 )while ICP of Group HES and Group RL significantly increased (P < 0.05 ). Two hours after resuscitation, MAP of Group HS began to decrease (P < 0.05 ). Four hours after resuscitation, only Group HSH can maintain an higher MAP and lower ICP. MDA and SOD levels in Group HSH were evidently lower than other groups at four hours after resuscitation (P < 0. 05). Pathological examination revealed less injury in Group HSH than other groups. Conclusion HSH could effectively resuscitate hemorrhagic shock, decrease ICP, reduce oxygen free radicals levels in brain tissue and relieve tissue ischemia/reperfusion injury. Key words: hypertonic sodium chloride; hydroxyethyl starch; acute intracranial hypertension; hemorrhagic shock

Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure*

To compare the effects of equimolar doses of 20% mannitol solution and of 7.45% hypertonic saline solution (HSS) in the treatment of patients with sustained elevated intracranial pressure (ICP). Parallel, randomized, controlled trial. Two intensive care units in a university hospital. A total of 20 stable patients with a sustained ICP of >20 mm Hg secondary to traumatic brain injury (n = 17) or stroke (n = 3). A single equimolar infusion (255 mOsm dose) of either 231 mL of 20% mannitol (mannitol group; n = 10 patients) or 100 mL of 7.45% hypertonic saline (HSS group; n = 10 patients) during 20 mins of administration. ICP, arterial blood pressure, cerebral perfusion pressure, blood flow velocities of middle cerebral artery using continuous transcranial Doppler, brain tissue oxygen tension, serum sodium and osmolality, and urine output during a study period of 120 mins. The two treatments equally and durably reduced ICP during the experiment. At 60 mins after the start of the infusion, ICP was reduced by 45% +/- 19% of baseline values (mean +/- sd) in the mannitol group vs. 35% +/- 14% of baseline values in the HSS group. Cerebral perfusion pressure and diastolic and mean blood flow velocities were durably increased in the mannitol group, resulting in lower values of pulsatility index at the different times of the experiment (p < .01 vs. HSS). No major changes in brain tissue oxygen tension were found after each treatment. Mannitol caused a significantly greater increase in urine output (p < .05) than HSS, although there was no difference in the vascular filling requirement between the two treatments. HSS caused a significant elevation of serum sodium and chloride at 120 mins after the start of the infusion (p < .01). A single equimolar infusion of 20% mannitol is as effective as 7.45% HSS in decreasing ICP in patients with brain injury. Mannitol exerts additional effects on brain circulation through a possible improvement in blood rheology. Pretreatment factors, such as serum sodium, systemic hemodynamics, and brain hemodynamics, thus should be considered when choosing between mannitol and HSS for patients with increased ICP.

Perioperative Hypertonic Saline May Reduce Postoperative Infections and Lower Mortality Rates

To determine the effects of hypertonic saline (HS) as fluid resuscitation during or after major spinal surgery. We hypothesized that the administration of HS perioperatively would decrease morbidity and mortality rates. A two-year retrospective, pair-matched, case-control study of adult patients (57 pairs matched 1:1) admitted to the intensive care unit (ICU) after major spinal procedures in a tertiary- and quaternary-care university medical center. Patients were matched for year of operation, operation site and magnitude, age, and sex. Each pair consisted of a patient who received HS either intraoperatively or postoperatively (Study patient) and a Control patient (isotonic fluids). No significant differences were seen in the underlying diseases. Neither the percentage of patients extubated in the operating room (OR) (Study, 44%; Control, 51%) nor the total time of intubation differed in the two groups. Patients receiving HS were in the operating room slightly longer. Length of stay (LOS) in the ICU was a median of 22 h in both groups. Hospital LOS was 7.7 +/- 6.1 days in the HS group and 7.3 +/- 3.5 days in the Control group (p = 0.98). Three infections occurred in the HS group and 11 in the Control group (p = 0.04). The total number of patients with one or more other complications was 11 in the HS group and 16 in the Control group (p = 0.19). Death occurred in two patients in the HS group and seven patients in the Control group (p = 0.08). Perioperative use of HS in major spinal surgery was associated with fewer postoperative infections, as well as trends toward fewer complications and a lower mortality rate. Further studies with strict protocols are warranted.

Effect of hypertonic saline concentration on cerebral and visceral organ water in an uninjured rodent model

Hypertonic saline has been shown to be an effective osmotic agent to reduce brain water and hence brain volume and intracranial pressure. A direct correlation between dose and effect has been demonstrated, but no studies have compared the effects of different concentrations of the same osmotic load of hypertonic saline over time. We compared the effects of different tonicity of infused hypertonic saline on cerebral, lung, and small bowel water extraction over time under controlled conditions. Laboratory study. Medical school. Male Wistar rats (280-450 g). Anesthetized rats were randomized to a 15-min intravenous bolus infusion of 0.9% NaCl or five equisodium but different concentrations of hypertonic saline: 4.2%, 7.5%, 10%, 23.4%, and 30%. Following infusion, animals remained anesthetized for 60, 180, or 300 mins without additional fluids given (n > or = 6 per group). Blood was sampled, total urine output was measured, and the animal was then killed under deep anesthesia. Cerebral, lung, and small bowel water contents were derived by wet/dry weight measures. After 60 mins, hypertonic saline administered at 50 mosm/kg resulted in an increase in serum osmolarity in all hypertonic saline groups (p < .05 vs. normal saline), with a significantly greater increase measured using 23.4% or 30% hypertonic saline (23.4%, 365.0 +/- 8.8 mosm/L, p < .05 vs. other lesser hypertonic saline doses). The durable effect was present throughout the 300-min period by all but the lowest hypertonic saline (4.2% NaCl). Lung but not small bowel organ water was diminished by hypertonic saline. Brain water content (79.1 +/- 0.2% in normal saline controls) was, however, significantly reduced. Hypertonic saline is effective in reducing organ water content in a setting of preserved blood-brain barrier but is not as effective in visceral organs. At equiosmotic doses of hypertonic saline, concentration plays no substantial role in altering serum osmolarity but appears to benefit duration of action. At very high concentrations, such as 23.4% NaCl, additional water extraction is also manifested. At such high concentration of NaCl, tonicity, indeed, matters, especially in water shifts across the blood-brain barrier.

The Effect of 7.2% Hypertonic Saline Solution with 6% Dextran 70 on Cardiac Contractility as Observed by an Echocardiography in Normovolemic and Anesthetized Dogs

We studied the effect of a small volume of 7.2% hypertonic saline solution (HSS) or HSS with 6% dextran 70 (HSD) on hemodynamic status, especially on cardiac contractility, in anesthetized dogs using the left ventricular end-systolic volume index (ESVI) and ejection fraction (EF), which can be obtained in noninvasive echocardiography. In the present study, the mean values of ESVI were unaffected by HSS and HSD infusion, whereas the left ventricular end-diastolic volume index (EDVI) was markedly and significant increased. As a result of the changes in EDVI but not in ESVI, EF increased transiently and significantly in the HSS and HSD group, whereas no such significant change was observed in the dogs that received isotonic saline solution. In addition, as a result of the increases in cardiac index but not arterial pressure, system vascular resistances (SVR) decreased transiently and significantly in the HSS and HSD groups, whereas no such significant change was observed in the ISS group. Therefore, the positive inotropic effects of HSS and HSD may be attributable to the increase in left ventricular preload and decreases in SVR rather than direct changes in myocardial contractility.