Effects Of Hypertonic Saline Resuscitation Research Articles

Beneficial Effect of Hypertonic Saline Resuscitation in a Porcine Model of Severe Acute Pancreatitis

Hypertonic saline (HTS) solution resuscitation has been used in a variety of clinical settings. The aim of this study was to assess the effect of HTS resuscitation on hemodynamics, systemic oxygenation, and organ damage in a porcine model of severe acute pancreatitis. Eighteen anesthetized and mechanically ventilated pigs were divided into 3 groups: HTS group, lactated Ringer solution (LR) group, and sham-operated group. Severe acute pancreatitis was induced in the first 2 groups by injecting 5% sodium taurocholate into the pancreatic duct, and the investigation period was 12 hours. Hemodynamic parameters, urine output, oxygenation parameters, and serum parameters were recorded consecutively. Finally, histologic examinations of the kidney, intestine, pancreas, and lung were performed. In the HTS group, cardiac output decreased less significantly compared with the LR group. Furthermore, aspartate aminotransferase, creatinine, and lactate levels increased significantly in all animals with severe acute pancreatitis, but the increasing tendency was slower in the HTS group. Nevertheless, the histopathologic analysis revealed similar injuries of the kidney, intestine, pancreas, and lung between the HTS and LR groups. Early administration of HTS generally improves hemodynamics and peripheral oxygenation. Despite these normalized parameters, organ damage could not be diminished to a significant degree during observation.

Hypertonic sodium resuscitation after hemorrhage improves hemodynamic function by stimulating cardiac, but not renal, sympathetic nerve activity

Small volume hypertonic saline resuscitation can be beneficial for treating hemorrhagic shock, but the mechanism remains poorly defined. We investigated the effects of hemorrhagic resuscitation with hypertonic saline on cardiac (CSNA) and renal sympathetic nerve activity (RSNA) and the resulting cardiovascular consequences. Studies were performed on conscious sheep instrumented with cardiac (n=7) and renal (n=6) sympathetic nerve recording electrodes and a pulmonary artery flow probe. Hemorrhage (20 ml/kg over 20 min) caused hypotension and tachycardia followed by bradycardia, reduced cardiac output, and abolition of CSNA and RSNA. Resuscitation with intravenous hypertonic saline (1.2 mol/l at 2 ml/kg) caused rapid, dramatic increases in mean arterial pressure, heart rate, and CSNA, but had no effect on RSNA. In contrast, isotonic saline resuscitation (12 ml/kg) had a much delayed and smaller effect on CSNA, less effect on mean arterial pressure, no effect on heart rate, but stimulated RSNA, although the plasma volume expansion was similar. Intracarotid infusion of hypertonic saline (1 ml/min bilaterally, n=5) caused similar changes to intravenous administration, indicating a cerebral component to the effects of hypertonic saline. In further experiments, contractility (maximum change in pressure over time), heart rate, and cardiac output increased significantly more with intravenous hypertonic saline (2 ml/kg) than with Gelofusine (6 ml/kg) after hemorrhage; the effects of hypertonic saline were attenuated by the β-receptor antagonist propranolol (n=6). These results demonstrate a novel neural mechanism for the effects of hypertonic saline resuscitation, comprising cerebral stimulation of CSNA by sodium chloride to improve cardiac output by increasing cardiac contractility and rate and inhibition of RSNA.

Effect of Hypertonic Saline Resuscitation on CD4+CD25+ Regulatory T Cells and γδ T Cells After Hemorrhagic Shock and Resuscitation in Relation to Apoptosis and iNOS

Hemorrhagic shock and resuscitation induce immunosuppression. CD4CD25 regulatory T cells and gammadeltaT cells may affect these immunosuppressive conditions. Hypertonic saline resuscitation reduces damage to organs and apoptosis and also restores immunosuppressive condition. We investigated how hypertonic saline resuscitation affected the induction of CD4CD25 regulatory T cells and gammadeltaT cells, and their apoptosis after hemorrhagic shock and resuscitation, and its relationship to inducible nitric oxide synthase (iNOS) (nitric oxide production). Male inbred C57BL6/J mice 8-week to 12-week-old as wild type and iNOS gene knock out (iNOS-/-), weighing 20 g to 35 g, were used. Hemorrhagic shock model of +/-40 mm Hg for 60 minutes was setup. Animals were randomly assigned to the following four resuscitation group: (1) wild HS: resuscitation with hypertonic saline (4 mL/Kg of 7.5% NaCl) and shed blood (SB), (2) wild 2LR: resuscitation with lactated Ringer's solution (two times the volume of the SB) and SB, (3) iNOS knockout HS, and (4) iNOS knockout 2LR. Untreated groups for wild and iNOS knockout mice were designated as control groups. Samples of thymus and spleen were harvested at 2 hours, 6 hours, 24 hours, and 48 hours after resuscitation. CD4CD25 regulatory T cells and gammadeltaT cells were analyzed using three-color flow cytometry. (1) gammadelta T cells increased earlier at 24 hours and CD4CD25 regulatory T cells increased later at 48 hours compared with controls in spleen of wild type (p < 0.01). (2) Hypertonic saline resuscitation suppressed gammadelta T cells compared with 2LR at 24 hours in iNOS knockout mice in spleen (p < 0.05). Hypertonic saline resuscitation increased apoptosis of CD4CD25 regulatory T cells at 48 hours in iNOS knockout mice in spleen (p < 0.01). (3) CD4CD25 regulatory T cells of iNOS knockout both in HS and 2LR groups at 48 hours decreased compared with wild type both in HS and 2LR groups in spleen (p < 0.01). (4) Apoptotic gammadelta T cells both in spleen and thymus in iNOS knockout mice at 48 hours increased compared with those in wild type (p < 0.05, respectively, except gammadelta T cells 2LR in spleen: p = 0.058). gammadelta T cells increased earlier at 24 hours, whereas CD4CD25 regulatory T cells increased later at 48 hours in spleen of wild type. Hypertonic saline was effective without the presence of iNOS, i.e., decreased gammadelta T cells at 24 hours and increased apoptosis of CD4CD25 regulatory T cells at 48 hours. CD4CD25 regulatory T cells at 48 hours without iNOS decreased compared with those of wild type. gammadelta T cells at 48 hours induced apoptosis under the condition without iNOS in spleen and thymus. iNOS worked as an accelerating factor for immunosuppressive condition, affected apoptosis, and immunoenhancing effect by hypertonic saline.

Effects of hypertonic saline on T-lymphocyte subpopulations in patients with traumatically hemorrhagic shock

Objective To investigate the potential and early effect of hypertonic saline resuscitation on Tlymphocyte subpopulations in patients with traumatically hemorrhagic shock.Method Eighty-two patients with acute traumatically hemorrhagic shock admitted from Department of Emergency，Beijing Tongren Hospital，from December 2006 to July 2008 were randomly divided into：hypotonic saline(HS)group(n=43)and Lactated Ringer's solution(LR)group(n=39).The criteria of eligible patients were systolic blood pressure＜90mm Hg at admission with definite evidence of blood loss.Patients with immune system diseases and those who died within 24 hours of admission were excluded.Patients in HS group received intravenous administration of 200 mL of 7.5% sodium chloride withhin 15～20 minutes，and LR group received routine therapy with Lactated Ringer's solution.Blood pressure and heart rate were recorded 10，20，and 60 minutes after the start of resuscitation and compared between two groups.Before and 24 hours after treatment，peripheral blood levels of T-lymphocyte subpopulationsincluding CD3+，CD4+，and CD8+ were measured by using direct immunofluorescence test and compared between two groups.The inter-group comparison was carried out by using independent sample t-lest and intragroup comparison using paired t-test.The numabers of operation，complication cases and death cases were conducted by using X2 test.SPAS version 11.0 software was used for statistical analysis.Results The volume of solution infused in HS group was(3820±623)mL and in LR group was(5430±1254)mL(P＜0.05).At 10 and 20 minutes after the sdministration of solution.the mean blood pressures in HS group were both significantly higher than those in LR group(P＜0.01).The levels of CD3+and CD4+lymphocytes in peripheral blood in HS group 24 hours after treatment were sinificantly higher than those in LR group(P＜0.01).Totally，63(76.8%)patients were cured and 19(23.2%)patients died.ARDS occurred in 10 patients and MODS occurred in 14 patiellts.The mortality，and the rates of ARDS and MODS in HS group were sinificantly higher than those in LP group(P＜0.05).Conclusiom In patients with acute traumatically hemorrhagic shock.HS can increase the effective circulating vol.ume，ameliorate the perfusion of tissues and organs，improve the immune fuction of T-lymphocytes，decrease the rats of ABDS and MODS，mad decrease the morality.HS is more effective than routine solution used for resuscitation. Key words: Hemorrhagic shock; Trauma; Hypertonic saline; T-lymphocyte subpopulations

Hypertonic saline resuscitation maintains a more balanced profile of T-lymphocyte subpopulations in a rat model of hemorrhagic shock

To investigate the potential and early effect of hypertonic saline resuscitation on T-lymphocyte subpopulations in rats with hemorrhagic shock. A model of rat with severe hemorrhagic shock was established in 18 Sprague-Dawley (SD) rats. The rats were randomly divided into Sham group, HTS group (hypertonic saline resuscitation group) and NS group (normal saline resuscitation group). Each group contained 6 rats. The CD4(+) and CD8(+) subpopulations of T-lymphocytes in peripheral blood were detected respectively before shock and after resuscitation by double antibody labelling and flow cytometry. In the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the CD4(+) lymphocytes of peripheral blood in HTS and NS groups markedly increased. Small volume resuscitation with HTS also induced peripheral CD8(+) lymphocytes to a certain extent, whereas NS resuscitation showed no effect in this respect. Consequently, compared with Sham and HTS groups, CD4(+)/CD8(+) ratio of peripheral blood in NS group was obviously increased, and showed statistically differences. In this model of rat with severe hemorrhagic shock, small volume resuscitation with HTS is more effective than NS in reducing immunologic disorders and promoting a more balanced profile of T-lymphocyte subpopulations regulating network.

HYPERTONIC SALINE RESUSCITATION REDUCES DAMAGE OF THE LIVER IN THE MOUSE MODEL OF HEMORRHAGIC SHOCK

We examined the effect of hypertonic saline resuscitation on histological damage of the liver after hemorrhagic shock and resuscitation in mice. Methods: Male BALB/c mice weighing 24 to 34 g were anesthetized and the left femoral artery was cannulated and blood was withdrawn until a mean arterial pressure of 40 ± 5 mmHg was reached. These levels of hypotension were sustained for 90 min, and resuscitation was made as follows: Sham; animals were anesthetized and catheter was inserted for 90 min, HS+SB; hemorrhage shock for 90 min and resuscitated with hypertonic saline (4 ml/Kg of 7.5% NaCl:HS) and shed blood (SB) at the same time, 2LR+SB; hemorrhage shock for 90 min and resuscitated with lactatedRinger's solution (2 times the volume of the shed blood) and SB.Samples were harvested at 2, 6, 24 and 48 h after hemorrhage and resuscitation. Injury score was defined as the extent of injury of the histological damage of the liver assessed with destroyed hepatocytes group formation, neutrophil infiltration, lipid follicle, vanishing nuclei of the hepatocytes, ballooning of the hepatocytes as follows. 0.5 = minimal injury, 1.0 = mild injury, 2.0 = moderate Injury, 3.0 = severe injury. Results: Histological damage shows the highest score in 2LR+SB group at 2h and HS+SB at 2h group shows significant decrease than 2LR+SB group at 2h (P < 0.01). Conclusion: HS resuscitation reduces the histological damage of the liver at 2h and the small intestine at 6h (published data) after hemorrhagic shock and resuscitation. These findings may have important role in development ofARDS and MOF after hemorrhagic shock and resuscitation.

The Immunomodulatory Effects of Hypertonic Saline Resuscitation in Patients Sustaining Traumatic Hemorrhagic Shock

To investigate the potential immunologic and anti-inflammatory effects of hypertonic saline plus dextran (HSD) in hemorrhagic trauma patients. Unbalanced inflammation triggered by shock has been linked to multiorgan dysfunction (MOD) and death. In animal and cellular models, HSD alters the inflammatory response to shock, attenuating MOD and improving outcome. It remains untested whether HSD has similar effects in humans. A single 250-mL dose of either HSD (7.5% NaCl, 6% dextran-70) or placebo (0.9% NaCl) was administered to adult blunt trauma patients in hemorrhagic shock. The primary outcome was to measure changes in immune/inflammatory markers, including neutrophil activation, monocyte subset redistribution, cytokine production, and neuroendocrine changes. Patient demographics, fluid requirements, organ dysfunction, infection, and death were recorded. A total of 27 patients were enrolled (13 HSD) with no significant differences in clinical measurements. Hyperosmolarity was modest and transient, whereas the immunologic/anti-inflammatory effects persisted for 24 hours. HSD blunted neutrophil activation by abolishing shock-induced CD11b up-regulation and causing CD62L shedding. HSD altered the shock-induced monocyte redistribution pattern by reducing the drop in "classic" CD14 and the expansion of the "pro-inflammatory" CD14CD16 subsets. In parallel, HSD significantly reduced pro-inflammatory tumor necrosis factor (TNF)-alpha production while increasing anti-inflammatory IL-1ra and IL-10. HSD prevented shock-induced norepinephrine surge with no effect on adrenal steroids. This first human trial evaluating the immunologic/anti-inflammatory effects of hypertonic resuscitation in trauma patients demonstrates that HSD promotes a more balanced inflammatory response to hemorrhagic shock, raising the possibility that similar to experimental models, HSD might also attenuate post-trauma MOD.

The effect of hypertonic saline resuscitation on responses to severe hemorrhagic shock by the skeletal muscle, intestinal, and renal microcirculation systems: seeing is believing

Background Decompensated hemorrhagic shock is often refractory to resuscitation, and we show here that it is associated with loss of vascular tone in skeletal muscle precapillary arterioles. We tested the hypothesis that microvascular derangements in the skeletal muscle, intestinal, and renal microcirculation systems would be reversed by initial hypertonic saline-dextran infusion. Methods Male Sprague-Dawley rats underwent precollicular brain stem transection without anesthesia for study. Parameters measured by in vivo videomicroscopy included cardiac output, mean arterial pressure, and microvascular responses in the skeletal muscle, ileum, and renal (i.e., the hydronephrotic kidney) microcirculation systems. Hemorrhaged was induced to a mean arterial pressure of 50 mm Hg until decompensation occurred. The rats were then initially resuscitated with (1) 4 mL/kg 7.5% NaCl in 6% dextran 70, (2) 33 mL/kg .9% NaCl in 6% dextran 70, or (3) 33 mL/kg .9% NaCl. Twenty minutes later they received shed blood plus 33 mL/kg .9% NaCl to maintain mean arterial pressure at baseline levels. Results Decompensated hemorrhagic shock decreased cardiac output to between 24% and 35% of baseline values and profoundly decreased microvascular blood flow to between 10% and 19% of baseline. At the completion of resuscitation cardiac output increased to greater than baseline in all groups. Microvascular blood flow increased toward baseline transiently but then progressively deteriorated to between 36% and 69% of baseline in the 3 tissues. There was no significant difference between the three resuscitative fluids. Conclusions Despite return of cardiac output to greater than baseline levels, muscle, intestinal, and renal microvascular blood flows remained significantly depressed. Hypertonic saline and/or dextran did not improve these deficits.

Hypertonic saline resuscitation reduces apoptosis and tissue damage of the small intestine in a mouse model of hemorrhagic shock.

The effect of hypertonic saline resuscitation on intestinal damage and the incidence of apoptosis after hemorrhagic shock were investigated. After anesthesia, male BALB/c mice weighing 24-34 g were hemorrhaged to the mean arterial pressure of 40 +/- 5 mmHg for 90 min. Animals were randomly assigned to four groups: 1) resuscitation with 4 mL/kg of 7.5% NaCl (hypertonic saline; HS) + shed blood (SB); 2) resuscitation with two times the volume of shed blood of lactated Ringer's solution (2LR) + SB; 3) sham (catheter only); or 4) control (no treatment). Intestinal damage was graded based on the extent of the vacuolation at the basal area of the intestinal villi. Apoptosis of the small intestines was examined with the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling method and with DNA laddering. Caspase-3 activation, heat shock protein (HSP) 70, and HSP40 were assessed by western blotting. Apoptosis of the small intestine and intestinal damage were significantly lower (P < 0.01) in the HS+SB group compared with the 2LR+SB group 2 h and 6 h after hemorrhagic shock and resuscitation, respectively. This corresponded with more DNA fragmentation in the small intestine of the 2LR+SB group compared with the HS+SB group 2 h after hemorrhage and resuscitation. In addition, we observed less caspase-3 activation in the small intestine of the HS+SB group compared with the 2LR+SB group at 2 h after resuscitation. The content of HSP40 and HSP70 in the HS+SB group was similar to that in controls, but slightly decreased in the 2LR+SB group. HS resuscitation reduced intestinal damage and apoptosis after hemorrhagic shock, suggesting that HS resuscitation may improve the outcome after hemorrhagic shock by reducing apoptosis and damage to the small intestine.

6 Hypertonic saline resuscitation: a new concept

Early treatment of haemorrhagic shock offers few theoretical, but many practical problems. Ideal or minimum volume replacement, and O 2 carrying capacity, are essential but logistics of pre-hospital management impose severe restrictions on what may, or may not, be done. Scoop-and-run, withheld fluid replacement and small volume resuscitation are alternative strategies under discussion at present. This review covers historical aspects of the introduction of small volume resuscitation, general properties required for its application, toxicological studies, available clinical and experimental data, physical, pharmacological and immune effects, mechanisms of action, prospects for clinical use. The controversial case of its interaction with uncontrolled bleeding is covered. It is concluded that the multiple physical, physiological and immune effects of hypertonic saline resuscitation, many of which require further research suggest potential clinical applications, in the primary treatment of hypovolemic shock, in cardiac surgery with cardiopulmonary bypass and in myocardial infarct. The interaction of hypertonic solutions with pro-inflammatory mediators has barely been scratched, and may induce a critical review of many concepts.

Hypertonic Saline Resuscitation Restores Hemorrhage-Induced Immunosuppression by Decreasing Prostaglandin E2and Interleukin-4 Production

It was previously shown that hypertonic saline (HTS) enhancesin vivoandin vitrocellular immune function of normal mice and reversesin vitroprostaglandin E2(PGE2)-induced immunosuppression of normal peripheral blood mononuclear cells. Hemorrhage induces immunosuppression despite adequate isotonic fluid resuscitation. The effects of HTS resuscitation on immunosuppression following hemorrhage were studied. A mouse model of hemorrhagic shock was used. Bleeding was performed through a catheter placed in the femoral artery. Phytohemagglutinin-induced splenocyte proliferation and interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, transforming growth factor β, and PGE2plasma levels were measured 2 and 24 hr following hemorrhage and resuscitation with lactated Ringer's and HTS.In vivocellular immune function was measured using a contact hypersensitivity test. Suppression of splenocyte proliferation (40%) 24 hr following hemorrhage occurred after lactated Ringer's resuscitation. HTS prevented immunosuppression.In vivocell-mediated immune function 24 hr after hemorrhage was improved by HTS. HTS-resuscitated animals showed significantly lower levels of IL-4 and PGE2, and slightly elevated levels of proinflammatory cytokines (IL-1, IL-2, and IL-6). HTS reverses hemorrhage-induced T-cell suppression by reducing the production and/or release of IL-4 and PGE2.