Comparative study on the effects of acetated Ringer's solution,lactated Ringer's solution,Ringer's solution,and 5% glucose-acetated Ringer's solution on canine hemorrhagic shock

The abilities of acetated Ringer's solution (AR), lactated Ringer's solution (LR), Ringer's solution (R), and 5% glucose-acetated Ringer's solution (AR-D) to improve canine hemorrhagic shock were investigated. All solutions studied were infused at 1 ml·kg⁻¹·min⁻¹ for 90 min after base excess (BE) reached about −13 mEq·l⁻¹ by maintaining the mean blood pressure (MBP) at 40 mmHg. MBP, renal blood flow (RBF), vertebral blood flow (VBF), and urinary output significantly increased after the start of infusion of AR, LR, R, and AR-D. The VBF and urinary output were particularly improved with AR-D. The arterial blood level of HCO ₃ ⁻ and BE were also increased after the start of infusion of AR, LR, and AR-D but not of R. AR infusion improved BE more effectively than LR. Although AR-D, AR, and LR increased HCO ₃ ⁻ , the blood pH did not increase in AR-D. The value of plasma acetate increased after the start of infusion of AR and AR-D but not of LR, and R. On the other hand, plasma lactate and pyruvate levels were higher with LR than with AR. The increase in the lactate/pyruvate ratio induced by LR was larger than that by AR. The plasma norepinephrine and epinephrine levels decreased after the start of all infusions. Plasma insulin and glucose levels were markedly increased after the start of AR-D infusion but were not affected by AR, LR, and R. These results indicate that the effectiveness of various infusion solutions such as AR, LR, R, and AR-D during canine hemorrhagic shock varies. AR-D may be useful for increasing both peripheral blood flow and urine output. AR may also be useful for improvement in metabolic acidosis and surgical diabetes induced by hemorrhagic shock.     

复方苹果酸钠对失血性休克大鼠小肠黏膜细胞凋亡的影响

目的观察复方苹果酸钠对失血性休克大鼠小肠黏膜细胞凋亡的影响。方法雄性SD大鼠48只,体重280~320g,随机分为假手术组(SS组)、生理盐水组(NS组)、复方乳酸钠组(RL组)和复方苹果酸钠组(RM组),每组12只。SS组为空白对照组,其余三组制作失血性休克模型,放血至MAP降为(40±5)mm Hg,休克60min后进行对应液体复苏,复苏后3h处死大鼠。检测小肠黏膜中B淋巴细胞瘤-2基因(Bcl-2)表达量和Bcl-2相关蛋白(Bax)含量,采用TUNEL法检测黏膜细胞凋亡情况,计算凋亡指数。检测小肠组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)浓度。取小肠黏膜做病理切片,观察病理改变。结果 NS、RL、RM组Bcl-2表达量明显低于SS组,Bax含量及凋亡指数明显高于SS组(P0.05);RM组Bcl-2表达量明显高于NS组和RL组,Bax含量及凋亡指数明显低于NS组和RL组(P0.05)。NS、RL、RM组SOD活性明显低于SS组,MDA浓度明显高于SS组(P0.05);RM组SOD活性明显高于NS组和RL组,MDA浓度明显低于NS组和RL组(P0.05)。病理组织切片显示RM组小肠黏膜损伤轻于NS组和RL组。结论复方苹果酸钠对于失血性休克大鼠小肠黏膜具有良好的抗凋亡作用,为临床晶体液的应用带来新的选择。     

Hepatic apoptosis after hemorrhagic shock in rats can be reduced through modifications of conventional Ringer's solution

BACKGROUND: Resuscitation with racemic lactated Ringer's solution induces cellular apoptosis. This study was conducted to determine if the elimination of D-lactate isomer would attenuate apoptosis in the liver, and to investigate the possible mechanisms. STUDY DESIGN: Sprague Dawley rats (n=30, 5 per group) were subjected to modified volume-controlled hemorrhage and randomized to the following groups: no hemorrhage (sham); no resuscitation (NR); resuscitation with racemic lactated Ringer's (DL-LR); L-isomer LR (L-LR); ketone (beta-hydroxybuturate) Ringer's (KR); or pyruvate Ringer's (PR). Animals were sacrificed 2 hours later and expressions of proapoptotic proteins (BAD), antiapoptotic (bcl-2) proteins, and poly-ADP ribose polymerase (PARP) cleavage in liver were analyzed by Western blotting. Contribution of the phosphatidylinositol 3-kinase/serine/threonine kinase (PI3k/Akt) pathway was assessed by measuring total and phosphorylated PI3K, Akt, BAD, and endothelial nitric oxide synthase (eNOS) proteins. The terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptotic cells. Liver ATP levels were measured using a luciferase reaction assay. RESULTS: Hemorrhage significantly decreased the hepatic ATP level and resuscitation improved it, but it returned to normal only in the L-isomer lactated Ringer's and ketone Ringer's groups. Expression of proapoptotic proteins was significantly lower in the pyruvate Ringer's and ketone Ringer's groups; L-isomer lactated Ringer's and pyruvate Ringer's resuscitation significantly increased bcl-2 expression. Poly-ADP ribose polymerase fragmentation and total number of apoptotic cells were significantly increased in the racemic lactated Ringer's group. There was no significant induction of Akt activity or changes in phosphorylated BAD, Akt, or eNOS levels. CONCLUSIONS: Resuscitation with racemic lactated Ringer's induces hepatic apoptosis, which is decreased if the D-isomer of lactate is eliminated. Apoptosis is reduced even more when lactate is substituted with beta-hydroxybutyrate or pyruvate. The beneficial effects are not through improvements in the energy status or activation of the PI3K/Akt pathway.     

Effects of hypertonic saline versus lactated Ringer's solution on cerebral oxygen transport during resuscitation from hemorrhagic shock

Hypertonic saline successfully restores systemic hemodynamics in dogs and humans with severe hemorrhagic shock and, in contrast to lactated Ringer's solution, does not increase intracranial pressure (ICP). This study compares cerebral oxygen delivery in 12 dogs subjected to hemorrhagic shock by the rapid removal of blood (mean arterial pressure of 40 mm Hg maintained for 30 minutes), and then resuscitated with lactated Ringer's solution (six dogs) or 7.5% saline solution (six dogs) to restore systolic arterial pressure. Both solutions effectively restored systemic hemodynamic stability, increasing cardiac output and systolic blood pressure while decreasing mean and diastolic arterial pressure and systemic vascular resistance. The ICP was significantly lower after resuscitation in the hypertonic saline group (p less than 0.05), but cerebral blood flow, which had decreased during shock, was not restored by either fluid, and cerebral oxygen transport fell further secondary to a hemodilutional reduction of hemoglobin. Although hypertonic saline may improve systemic hemodynamics and maintain a low ICP during resuscitation, it fails, as does Ringer's solution, to restore cerebral oxygen transport to prehemorrhagic shock levels.     

Volume replacement with lactated Ringer's or 3% hypertonic saline solution during combined experimental hemorrhagic shock and traumatic brain injury

BACKGROUND: The devastating effects of hypotension on head-trauma-related mortality are well known. This study evaluates the systemic and cerebral hemodynamic responses to volume replacement with 3% hypertonic saline (HSS) or lactated Ringer's solution (LR), during the acute phase of hemorrhagic shock (HS) associated with traumatic brain injury (TBI). METHODS: Fifteen dogs were assigned to one of three groups (n = 5, each) according to the volume replacement protocol, infused after TBI (brain fluid percussion, 4 atm) and epidural balloon to an intracranial pressure (ICP) higher than 20 mm Hg and HS, induced by blood removal to a mean arterial pressure (MAP) of 40 mm Hg in 5 minutes: Group HS+TBI+HSS (8 mL/kg of 3% HSS), HS+TBI+LR (16 mL/kg LR), and Group HS+TBI (controls, no fluids). We simulated treatment during prehospital and early hospital admission. Groups HS+ TBI and HS+TBI+LR received shed blood infusion to a target hematocrit of 30%. Measurements included shed blood volume, fluid volume infused to restore MAP, MAP, cardiac output, cerebral perfusion pressure, cerebral and systemic lactate, and oxygen extraction ratios. RESULTS: Fluid replacement with HSS 3% or LR promoted major hemodynamic benefits over control animals without luids. Cerebral perfusion pressure was higher than controls and similar between treated groups; however, HSS 3% infusion was associated with lower ICP during the "early hospital phase" and a higher serum sodium and osmolarity. CONCLUSION: In the event of severe head trauma and hemorrhagic shock, the use of HSS 3% and larger volumes of LR promote similar systemic and cerebral hemodynamic benefits. However, a lower ICP was observed after HSS 3% than after LR.     

Lactated Ringer's solution and hypertonic saline improve survival in uncontrolled hemorrhagic shock in female rats in metestrus

BACKGROUND: In the present investigation the effect of fluid treatment in uncontrolled hemorrhagic shock after massive splenic injury (MSI) was comparatively studied in male and female rats. MATERIALS AND METHODS: The anesthetized animals were randomly divided into three groups: in group 1 MSI was induced in males, in group 2 MSI was induced in females in proestrus, in group 3 MSI was induced in females in metestrus. Each group was divided into four subgroups: a) Sham-operated, b) MSI untreated (UT), c) MSI treated with 40 ml/kg lactated Ringer's solution (RL), and d) MSI treated with 5 ml/kg NaCl 7.5% (HTS). RESULTS: Total blood loss (TBL) in groups 1b, 2b, and 3b was 31.7 +/- 3.6%, 33.1 +/- 2.6%, and 36.7 +/- 2.6%, respectively, and mean survival time (MST) was 143.7 +/- 25.3 min, 174.8 +/- 10.4 min, and 67.8 +/- 11.4 min (P < 0.01 versus group 2b), respectively. TBL in groups 1c, 2c, and 3c increased to 52.4 +/- 5.5% (P < 0.02 versus UT), 48.6 +/- 1.6% (P < 0.02 versus UT), and 48.8 +/- 4.1% (P < 0.02 versus UT), respectively, and MST decreased to 126 +/- 19.4 min, (P < 0.05 versus UT), and 136.8 +/- 13.0 min (P < 0.05 versus UT) in groups 1c and 2c, respectively, and increased in group 3c to 120.4 +/- 23.3 min (P < 0.05 versus UT). TBL in groups 1d, 2d, and 3d was 31.3 +/- 4.8%, 38.0 +/- 4.2%, and 40.6 +/- 3.7%, respectively, and MST increased to 198.5 +/- 13.9 min (P < 0.05 versus UT) in group 1d, decreased to 128.4 +/- 17.2 min (P < 0.01) in group 2d, and increased to 102.6 +/- 19.0 min (P < 0.002 versus group 1d) in group 3d. CONCLUSIONS: RL infusion significantly increased blood loss in all three groups, reduced survival time in males and female rats in proestrus, but significantly improved survival in females in metestrus. HTS treatment did not alter blood loss in all three groups, but significantly improved survival in females in metestrus and males.     

Hepatic and pulmonary apoptosis after hemorrhagic shock in swine can be reduced through modifications of conventional Ringer's solution

BACKGROUND: Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in vitro and in small animal experiments, have not been confirmed in large animal models. Our hypothesis was that in a clinically relevant large animal model of hemorrhage, resuscitation with racemic lactated Ringer's solution would induce cellular apoptosis, which can be attenuated by elimination of d-lactate. METHODS: Yorkshire swine (n = 49, weight 40-58 kg) were subjected to uncontrolled (iliac arterial and venous injuries) and controlled hemorrhage, totaling 40% of estimated blood volume. They were randomized (n = 7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L-LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was identical to LR except for equimolar substitution of lactate with beta-hydroxybutyrate. Resuscitation was performed in three phases, simulating (1) prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood gasses, circulating cytokines (TNF-alpha, IL-1, -6, -10), and markers of organ injury were serially measured. Metabolic activity of brain, and liver, was measured with microdialysis. Four hours postinjury, organs were harvested for Western blotting, ELISA, TUNEL assay, and immunohistochemistry. RESULTS: All resuscitation strategies restored blood pressure, but clearance of lactic acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased during shock and improved with resuscitation, without any significant inter-group differences. Levels of cytokines in circulation were similar, but tissue levels of TNF in liver and lung increased six- and threefolds (p < 0.05) in NR group. In liver, all resuscitation strategies significantly decreased TNF levels compared with the NR group, but in the lung resuscitation with lactated Ringer (DL and L isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation with other solutions. CONCLUSIONS: In this large animal model of hemorrhagic shock, resuscitation with conventional (racemic) LR solution increased apoptotic cell death in liver and lung. This effect can be prevented by simple elimination of D-lactate from the Ringer's solution.     

Tissue oxygen monitoring during hemorrhagic shock and resuscitation: a comparison of lactated Ringer's solution,hypertonic saline dextran,and HBOC-201

BACKGROUND: The ideal resuscitation fluid for the trauma patient would be readily available to prehospital personnel, universally compatible, effective when given in small volumes, and capable of reversing tissue hypoxia in critical organ beds. Recently developed hemoglobin-based oxygen-carrying solutions possess many of these properties, but their ability to restore tissue oxygen after hemorrhagic shock has not been established. We postulated that a small-volume resuscitation with HBOC-201 (Biopure) would be more effective than either lactated Ringer's (LR) solution or hypertonic saline dextran (HSD) in restoring baseline tissue oxygen tension levels in selected tissue beds after hemorrhagic shock. We further hypothesized that changes in tissue oxygen tension measurements in the deltoid muscle would reflect the changes seen in the liver and could thus be used as a monitor of splanchnic resuscitation. METHODS: This study was a prospective, blinded, randomized resuscitation protocol using anesthetized swine (n = 30), and was modeled to approximate an urban prehospital clinical time course. After instrumentation and splenectomy, polarographic tissue oxygen probes were placed into the liver (liver PO2) and deltoid muscle (muscle PO2) for continuous tissue oxygen monitoring. Swine were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg over 20 minutes, shock was maintained for another 20 minutes, and then 100% oxygen was administered. Animals were then randomized to receive one of three solutions: LR (12 mL/kg), HSD (4 mL/kg), or HBOC-201 (6 mL/kg). Physiologic variables were monitored continuously during all phases of the experiment and for 2 hours postresuscitation. RESULTS: At a MAP of 40 mm Hg, tissue PO2 was 20 mm Hg or less in both the liver and muscle beds. There were no significant differences in measured liver or muscle PO2 values after resuscitation with any of the three solutions in this model of hemorrhagic shock. When comparing the hemodynamic effects of resuscitation, the cardiac output was increased from shock values in all three animal groups with resuscitation, but was significantly higher in the animals resuscitated with HSD. Similarly, MAP was increased by all solutions during resuscitation, but remained significantly below baseline except in the group of animals receiving HBOC-201 (p < 0.01). HBOC-201 was most effective in both restoring and sustaining MAP and systolic blood pressure. There was excellent correlation between liver and deltoid muscle tissue oxygen values (r = 0.8, p < 0.0001). CONCLUSION: HBOC-201 can be administered safely in small doses and compared favorably to resuscitation with HSD and LR solution in this prehospital model of hemorrhagic shock. HBOC-201 is significantly more effective than HSD and LR solution in restoring MAP and systolic blood pressure to normal values. Deltoid muscle PO2 reflects liver PO2 and thus may serve as an index of the adequacy of resuscitation in critical tissue beds.     

Are lactated Ringer's solution and normal saline solution equal with regard to coagulation?

Crystalloids represent an attractive strategy to alleviate intravascular volume deficits. Crystalloid hemodilution was associated with hypercoagulability in in vitro and in vivo studies. The influence of different crystalloids on coagulation in the surgical patient is not well studied. In a prospective, randomized study in patients undergoing major abdominal surgery, we used either lactated Ringer's solution (RL) (n = 21) or 0.9% saline solution (SS) (n = 21) exclusively for intravascular volume replacement over 48 h to maintain central venous pressure between 8 and 12 mm Hg. Activated thrombelastography (TEG) using different activators (intrinsic TEG, extrinsic TEG, heparinase TEG, aprotinin TEG) was used to measure coagulation time, clot formation time, and maximum clot firmness. Measurements were performed after induction of anesthesia (T0), immediately after surgery (T1), 5 h after surgery (T2), and on the morning of the first (T3) and second (T4) postoperative days. RL 18,750 +/- 1890 mL and 17,990 +/- 1790 mL of SS were infused during the study period. Acidosis was seen only in the SS-treated group. Blood loss was not different between the groups. Fibrinogen and antithrombin III decreased similarly at T1 and T2 in both groups, most likely because of hemodilution. Differences in TEG data from normal baseline were seen only immediately after surgery and 5 h thereafter, indicating mild hypercoagulability in the intrinsic TEG (RL, from 147 +/- 130 s to 130 +/- 11 s; SS, from 146 +/- 12 s to 131 +/- 12 s). There were no differences in coagulation between RL- and SS-treated patients. We conclude that in major abdominal surgery intravascular volume replacement with crystalloids resulted in only moderate and abbreviated changes in coagulation. No differences in activated TEG and blood loss were seen between an RL- and an SS-based intravascular volume replacement regimen. IMPLICATIONS: In 42 patients undergoing major abdominal surgery, either lactated Ringer's solution or 0.9% saline solution were exclusively used for volume therapy for 48 h. Activated thrombelastography revealed some mild hypercoagulability after surgery. No differences in coagulation were seen between the two intravascular volume replacement strategies.     

Prospective, randomized trial of hypertonic sodium lactate versus lactated Ringer's solution for burn shock resuscitation

We prospectively randomized 51 adult burned patients on admission to study fluid, electrolyte, and physiologic parameters during burn resuscitation with the use of hypertonic saline (HSL, Na 250 mEq/L, 514 mOsm) or lactated Ringer's solution (LR, Na 130 mEq/L, 268 mOsm). Patients suffered at least 20% total body surface area burns (BSA); the mean BSA injury was 36.7% BSA, with a range of 20 to 74% BSA. All patients were admitted to our Burn Center within at least 12 hours of injury. Laboratory studies included frequent determinations of serum chemistries including osmolalities, and continuous 24-hour urine collections for electrolytes and osmolality determinations. Fluid requirements (cc/kg/% BSA), urine output (cc/kg/hr), sodium intake and excretion (mEq/kg/% BSA), serum and urine osmolality (mOsm/kg), serum creatinine (mg/dl), body weight (kg), and enteral intake (cc/24 hrs and calories/24 hrs) were analyzed for comparison at 24-hour intervals following burn injury. Using Student's t-test, significance was attributed to a p less than 0.05. Nonparametric methods were used to compare non-normalized data. Regression analysis was used to compare sodium intake (mEq/kg) and fluid intake (cc/kg) between the HSL and the LR groups in relation to % BSA. Our data show no advantage of HSL over conventional therapy with LR for burn resuscitation. We were not able to demonstrate decreased fluid requirements, improved tolerance of feedings, or decrease in per cent weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early hemodynamic and renal effects of hemorrhagic shock resuscitation with lactated Ringer's solution, hydroxyethyl starch, and hypertonic saline with or without 6% dextran-70

BACKGROUND: Considering the renal effects of fluid resuscitation in hemorrhaged patients, the choice of fluid has been a source of controversy. In a model of hemorrhagic shock, we studied the early hemodynamic and renal effects of fluid resuscitation with lactated Ringer's (LR), 6% hydroxyethyl starch (HES), and 7.5% hypertonic saline (HS) with or without 6% dextran-70 (HSD). MATERIALS AND METHODS: Forty-eight dogs were anesthetized and submitted to splenectomy. An estimated 40% blood volume was removed to maintain mean arterial pressure (MAP) at 40 mm Hg for 30 min. The dogs were divided into four groups: LR, in a 3:1 ratio to removed blood volume; HS, 6 mL kg(-1); HSD, 6 mL kg(-1); and HES in a 1:1 ratio to removed blood volume. Hemodynamics and renal function were studied during shock and 5, 60, and 120 min after fluid replacement. RESULTS: Shock treatment increased MAP similarly in all groups. At 5 min, cardiac filling pressures and cardiac performance indexes were higher for LR and HES but, after 120 min, there were no differences among groups. Renal blood flow and glomerular filtration rate (GFR) were higher in LR at 60 min but GFR returned to baseline values in all groups at 120 min. Diuresis was higher for LR at 5 min and for LR and HES at 60 min. There were no differences among groups in renal variables 120 min after treatment. CONCLUSIONS: Despite the immediate differences in hemodynamic responses, the low-volume resuscitation fluids, HS and HSD, are equally effective to LR and HES in restoring renal performance 120 min after hemorrhagic shock treatment.     

Intraoperative fluid therapy by lactated Ringer's solution with various concentrations of potassium

Lactated Ringer's solutions, whose concentration of potassium was 10 or 20 mEq.l-1, were infused into 10 and 9 patients undergoing surgical operations under general anesthesia, respectively. Effects of these fluid therapies on serum potassium and blood sugar were studied comparing with the effect of infusion of regular lactated Ringer's solution. A decrease in serum potassium concentration seen with the regular lactated Ringer's solution during the surgery was minimized with the lactated Ringer's solutions of 10 or 20 mEq.l-1 of potassium. With the lactated Ringer's solutions of higher concentrations of potassium, an increase in blood sugar level, which was noted with the regular lactated Ringer's solution, was not observed although all the lactated Ringer's solutions contained 0.7% of glucose. Furthermore, base excess remained at a normal level in patients of high potassium groups, but it decreased in patients of the regular potassium group. Lactated Ringer's solutions of high potassium levels are useful to maintain serum potassium and glucose levels at more normal levels during surgical procedures under general anesthesia.     

减阻剂用于出血性休克复苏的实验研究

Drag reducing polymers （DRPs） provide large drag reductions iu turbulent flow at nanomolar concentrations of linear macropolymers,as polyethylene glycol, aloe vera polymer. DRPs have been shown to significantly enhance hemodynamics and improve microcirculation, make the red blood cells work harder and increase blood pressure , improve survival in hemorrhagie shock.     

Plasma and thoracic duct albumin kinetics during hemorrhage treated with lactated Ringer's solution

The rapid expansion of PV and ECF with Lactated Ringer's solution, whether alone or following a hemorrhage of 15% of blood volume, markedly alters the kinetics of albumin distribution between plasma and left TDF lymph in dogs.Lactated Ringer's infusion of 1100 ml increased TDF lymph flow nearly fivefold in all animals, but concurrent protein dilution resulted in only a threefold increase in the amount of TDF albumin delivery. This transient increase in TDF delivery of albumin ended in less than 1 hr, while the TDF flow continued at twofold levels for the next 4 hr.The immediate 4:1 volume replacement of shed blood with Lactated Ringer's solution resulted in near normal albumin kinetics between plasma and TDF lymph. Lactated Ringer's infusion alone produced an accelerated appearance of albumin specific activity within TDF lymph, while decreasing the overall disappearance rate of albumin specific activity from the intravascular space.It is postulated that transient hypervolemia created by rapid infusion of Lactated Ringer's solution increases visceral filtration of albumin into TDF lymph, but not total body capillary filtration. Additionally, it appears that the apparent decreased visceral filtration found after hemorrhage can be reversed to normal by 4:1 volume restitution with Lactated Ringer's solution.     

A case of anaphylactoid reactions to lactated Ringer's solution with 5% maltose

A 27-years-old man was admitted for correction of nasal fracture. He presented with circulatory collapse and generalised erythema on induction of general anesthesia and during preparation of intradermal test for identifying the offending agent. As both of these responses occurred during intravenous infusion of lactated Ringer's solution with 5% maltose, anaphylactoid responses to this intravenous solution were strongly suspected.