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.     

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.     

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)     

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.     

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.     

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.     

Delayed immune dysfunction following hemorrhagic shock and resuscitation

Immune system function is thought to be depressed after hemorrhagic shock. We evaluated the delayed effect of hemorrhagic shock on the immune system in rats with and without spleens and investigated the effect of the colloid hetastarch on reticuloendothelial system (RES) function. There were six groups: controls (N = 30, no shock), two groups of shocked animals resuscitated with either hetastarch (HES, N = 13) or lactated Ringer's (LR, N = 13); the remaining three groups were identical except that splenectomy had been performed (N = 16, N = 14, and N = 16, respectively). One week after shock and resuscitation, all groups were challenged with intravenous Streptococcus pneumoniae; quantitative blood and tissue (liver, lung, and spleen) cultures were then obtained. There were no differences between the HES and LR groups. In nonsplenectomized animals, colony counts in the blood, liver, lung, and spleen were significantly higher in shocked animals when compared with controls. Splenectomized rats had no significant differences between shocked groups and controls. These data demonstrate that delayed immune function is depressed in nonsplenectomized rats. Splenectomy causes more severe immune dysfunction than does shock. Also, in similar animals without splenectomy, hetastarch does not appear to alter delayed RES function.     

Hypertonic saline solution resuscitation in hemorrhagic shock dogs

Objective: To find out the optimal concentration,infusion rate and dosage of saline for resuscitation. Methods: Forty-five dogs were used to establish hypovolemic shock models. The dogs were resuscitated with saline of different concentrations and different dosages under different infusion rates, and the resuscitation results were compared. Results: The best concentration was 7.5%, the best rate of infusion 20 ml/min ( a volume equivalent to 15 % of the shed blood ) and the best dosage 5.71 ml/kg. The method was effective for resuscitation, the mean arterial pressure (MAP) could be elevated to 89 % of the baseline,and this MAP could be kept for more than one hour. Conclusions： Using 7.5% sodium chloride solution equivalent to 15% of the shed blood at an infusion rate of 20 ml/min can achieve a best resuscitation result.     

失血性休克后液体复苏的研究进展

背景 失血性休克是外伤死亡的主要原因.在重危病例的急救和围手术期的处理中,液体复苏起着关键性的治疗作用. 目的 就重度失血性休克后液体治疗方案的研究进展作一综述. 内容 除了传统的晶体液,近年来开发了诸多新品种的液体用于复苏,如丙酮酸钠溶液等.复苏方式的研究也在静脉复苏的基础上拓展到了腹腔复苏. 趋向 丙酮酸钠溶液以及腹腔复苏是近年来研究提出的新的复苏液体和复苏方案,通过已有的研究已经证实其积极的治疗作用.其应用于失血性休克的方法、时间、疗效等仍需更进一步研究.     

The effects of lactated Ringer's solution infusion on cardiac output changes after spinal anesthesia

We evaluated the effects of an infusion of lactated Ringer's (LR) solution on changes in cardiac output (CO) after spinal anesthesia. Seventy-five patients scheduled for lower extremity surgery under spinal anesthesia were studied. We measured CO (impedance cardiography method) and blood pressure for 25 min before and 30 min after spinal anesthesia. Patients were randomly assigned to three groups. In the No Infusion group, no LR solution was given during the period of measurements. The LR Before group received 12 mL/kg of LR solution within 20 min before spinal anesthesia. The LR After group received 12 mL/kg of LR solution within 20 min starting immediately after spinal anesthesia. After spinal anesthesia, CO decreased by 13.9% in the No Infusion group. In the LR Before group, CO increased after the infusion by 20% and returned to baseline value 30 min after spinal anesthesia. In the LR After group, CO increased after spinal anesthesia, and 30 min after spinal anesthesia, CO was 11.3% above baseline. We conclude that the decrease in CO after spinal anesthesia can be prevented by the infusion of an LR solution, with CO reaching the highest value while the infusion is running. IMPLICATIONS: We studied the effects of lactated Ringer's solution infusion on cardiac output changes after spinal anesthesia. If the patients received no infusion, cardiac output decreased after spinal anesthesia. However, if the patients received lactated Ringer's solution infusion, cardiac output was maintained.     

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.     

Lactated Ringer's is superior to normal saline in the resuscitation of uncontrolled hemorrhagic shock

BACKGROUND: Normal saline (NS) and lactated Ringer's solution (LR) continue to be used interchangeably for the resuscitation of hemorrhagic shock in some institutions. We hypothesized that, aside from hyperchloremic acidosis, NS resuscitation would be similar to that of LR in a swine model of uncontrolled hemorrhage. METHODS: Twenty swine weighing a mean of 37 kg underwent invasive line placement, midline celiotomy, and splenectomy. After a 15-minute stabilization period, we recorded a baseline mean arterial pressure (MAP) and created a grade V liver injury. The animals bled freely for 30 minutes after which we measured blood loss. We blindly randomized the swine to receive NS (10 animals) versus LR (10 animals) to achieve and maintain the baseline MAP for 90 minutes postinjury. Laboratory values were obtained at baseline and upon completion of the 2-hour study period. RESULTS: Initial blood loss was 25 mL/kg in the NS group and 22 mL/kg in the LR group (p = 0.54). Animals required 256.3 +/- 145.4 mL/kg of fluid in the NS group as compared with 125.7 +/- 67.3 mL/kg in the LR group (p = 0.04). The urine output was higher in the NS group (46.6 +/- 39.5 mL/kg versus 18.9 +/- 12.9 mL/kg, p = 0.04). Upon study completion, the NS group had a significant hyperchloremia (119 +/- 1.9 mEq/L versus 105 +/- 2.9 mEq/L, p < 0.01) with acidosis (7.28 +/- 0.12 versus 7.45 +/- 0.06, p < 0.01) in comparison to the LR group. In addition, resuscitation with NS resulted in significantly lower fibrinogen levels (99 +/- 21 mg/dL versus 123 +/- 20 mg/dL, p = 0.02). The serum lactate was 4.7 +/- 2.2 in the LR group and 1.7 +/- 1.7 in the NS swine (p < 0.01) at the end of the study. CONCLUSIONS: Resuscitation of uncontrolled hemorrhagic shock with NS requires significantly greater volume and is associated with greater urine output, hyperchloremic acidosis, and dilutional coagulopathy as compared with LR. Resuscitation with LR results in an elevation of the lactate level that is not associated with acidosis. Lactated Ringer's solution is superior to NS for the resuscitation of uncontrolled hemorrhagic shock in swine.     

Antioxidative resuscitation solution prevents leukocyte adhesion in the liver after hemorrhagic shock.

BACKGROUND: The generation of iron-dependent toxic oxygen radicals during the initial resuscitation from hemorrhagic shock was shown to be a relevant factor for the initiation of the inflammatory cascade. Therefore, this experimental study was designed to evaluate the effects of a deferoxamine-conjugated hydroxyethyl-starch solution (HES-DFO) on oxygen radical induced injury and microcirculatory alterations in the rat liver compared with resuscitation with regular hydroxyethyl-starch, lactated Ringer's solution (RL), or a gelatin-based solution. METHODS: After hemorrhage and random assignment to 1 hour of blood-free resuscitation with the aforementioned solutions, hepatic microcirculation and leukocyte adhesion characteristics were assessed by intravital fluorescence microscopy in anesthetized rats. Oxygen radical activity was estimated by determination of glutathione levels in liver homogenate and determination of thiobarbituric acid-reactive substances in plasma as markers of lipid peroxidation. RESULTS: Resuscitation by HES-DFO resulted in restoration of hemodynamic parameters compared with gelatin-based solution and HES. The hepatic microcirculation was severely altered 1 hour after resuscitation from shock in all groups indicated by sinusoidal narrowing and reduced sinusoidal blood flow. HES-DFO, however, attenuated leukocyte adhesion and improved velocity index in sinusoids as well as sinusoidal perfusion. The shock-associated generation of oxygen radicals during resuscitation was prevented by HES-DFO as indicated by restored glutathione and reduced thiobarbituric acid-reactive substances. CONCLUSION: The results suggest that HES-DFO effectively reduces oxygen radical formation during the initial resuscitation period, thus, attenuating pathologically enhanced leukocyte adhesion and improving hepatic microcirculation.     

Controlled resuscitation for uncontrolled hemorrhagic shock

OBJECTIVE: To test the hypothesis that controlled resuscitation can lead to improved survival in otherwise fatal uncontrolled hemorrhage. METHODS: Uncontrolled hemorrhage was induced in 86 rats with a 25-gauge needle puncture to the infrarenal aorta. Resuscitation 5 minutes after injury was continued for 2 hours with lactated Ringer's solution (LR), 7.3% hypertonic saline in 6% hetastarch (HH), or no fluid (NF). Fluids infused at 2 mL x kg(-1) x min(-1) were turned on or off to maintain a mean arterial pressure (MAP) of 40, 80, or 100 mm Hg in six groups: NF, LR 40, LR 80, LR 100, HH 40, and HH 80. Blood loss was measured before and after 1 hour of resuscitation. RESULTS: Survival was improved with fluids. Preresuscitation blood loss was similar in all groups. NF rats did not survive 4 hours. After 72 hours, LR 80 rats (80%) and HH 40 rats (67%) showed improved survival over NF rats (0%) (p < 0.05). Rebleeding increased with MAP. Attempts to restore normal MAP (LR 100) led to increased blood loss and mortality. CONCLUSION: Controlled resuscitation leads to increased survival compared with no fluids or standard resuscitation. Fluid type affects results. Controlled fluid use should be considered when surgical care is not readily available.     

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.     

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.