Ringer's Group Research Articles

Protective effects of hydroxyethyl starch on myocardial ischemia/reperfusion injury in rabbits

Objective To observe the effects of hydroethyl starch (HES 130/0.4) on serum interleukin-8, endothelin-l(ET-1) and myocardial myeloperoxidase activity (MP0) in rabbits subjected to ischemia-reperfusion, and to explore its possible mechanism. Method Thirty-six rabbits were randomly divided into three groups: lac-tated Ringer's solution group (group A, n= 12), 5% human albumin group (group B, n= 12) and 6% hy-droethyl starch group (group C, n= 12) Hie myodardial ischemia/reperfusion (MI/R) model was established by clamping left anterior descending coronary artery for 30 minutes followed by reperfusion for 180 minutes. Fifteen minutes prior to reperfusion, animals of these 3 given groups were ifused vis right internal jugular vein with 6 ml/kg lactated Ringer'solution, 5% human albumin and hydroethyl starch, respectively. Blood samples were obtained before occlusion (I_0),30 minutes after occlusion (I_1), 60 minutes (R_1) and 180 (R_2) minutes after reperfusion to determine the activities of serum lactate dehydrogenase (LDH), serum creatine phosphokinase (CPK), serum interleukin-8(IL-8) and endotheun-1 (ET-1).The size of myocardial infarction (MI),myocardial water content and myoloperoxidase activity (MPO) were examined as well.Statistical analyses were performed by using SPSS 12.0 software. Multiple comparisons were analyzed by using one-way analysis of variance (SNK- qtest). P ＜ 0.05 was considered statistically significant. Results The serum IDH, CPK,IL-8 and ET-1 weregradually increased after reperfusion, however, 180 min after reperfusion all serum biomarkers in 6% hydroethylstarch group (group C) were significantly lower than those in Iactated Ringer's solution group (group A) [(181 ±17) U/lvs. (334±39) U/L; (1927±205) U/L vs. (2987±326) U/L; (5.03±1.16) ng/L vs. (6.96±1.21) ng/L; (380±78.4) ng/L vs. (667.2±82.1) ng/L. all P ＜0.05], and than those in 5% human albu-min group (group B) [(181 ±17) U/L vs. (320±38) U/L; (1727 ±205) U/L vs. (2218 ±290) U/L; (5.03 ±1.16) ng/L vs. (5.90±1.03) ng/L; (380.9±78.4) ng/L vs. (615.6±80.2) ng/L, all P ＜0.05]. Theactivity of MPO of ischemic area in group C (0.20 ± 0.09 ng/L) was significantly lower than that in group A(0.48±0.15 ng/L) and in group B (0.37 ±0.12 ng/L) (P ＜ 0.05). Myocardial water content and infarct sizeof heart found in group C were significantly smaller than those in both group A and group B (P ＜ 0.05). Conclu-sions The 6% hydroethyl starch exhibits its protective effects on myocardial ischemia-reperfusion injury by pre-venting the production and release of serum IL-8 and ET-1, decreasing neutrophil infiltration capillary permeabilityand improving microvascular circulation. Key words: Hydroxyethyl starch; Reperfusion injury; Interleukin-8; Endothelin-1; Myeloperoxidase

The ameliorating effect of preoperative loading infusion with 4% succinylated gelatin solution on hemorheology of gastric cancer patients during perioperative period

Objective To investigate the effect of loading infusion with succinylated gelatin(GEL) solution before surgery on hemorheology of patients with gastric cancer during perioprative period. Methods Forty patients undergoing gastric cancer radical surgery were randomly divided into 2 groups (n=20): GEL solution group (GEL group) and Ringer's Lactated solution group(RL group). Twenty people received health examination were selected as normal control group. The two kinds of solution were respectively infused at a dose of 15 ml/kg over a period of 30 rain before surgery (loading infusion, LI). Blood samples were taken for determination of hemorheology variables before LI(T_0, baseline), the end of LI(T_1), 1 h after the end of Ll(T_2)and 1 h after the end of surgery (T_3). Results The blood viscosity, plasma viscosity, erythrocyte aggregation index (EAI)and fibrinogen were higher than those in normal control group (P<0.05). The blood viscosity, plasma viscosity, EAI, fibrinogen and Hct decreased significantly as compared to the baseline values at T_0 in GEL group(P<0.05). The blood viscosity at low shear rate and EAI increased significantly as compared to the baseline values at T_0 in RL group (P<0.05). The blood viscosity, plasma viscosity, EAI, fibrinogen and Hct were lower than those in RL group at T_2 and T_3(P<0.05). Conclusion Blood of patients with gastric cancer presentes hyperviscosity state.GEL solution can ameliorate hemorheology variables and alleviate hyperviscosity state during perioperative period. Key words: Gelatin; Fluid therapy; Hemorheology; Gastric neoplasms

Fluid Management for Laparoscopic Colectomy: A Prospective, Randomized Assessment of Goal-Directed Administration of Balanced Salt Solution or Hetastarch Coupled with an Enhanced Recovery Program

No consensus exists regarding the optimal fluid (crystalloid or colloid) or strategy (liberal, restricted, or goal directed) for fluid management after colectomy. Prior assessments have used normal saline. This is the first assessment of standard, goal-directed perioperative fluid management with either lactated Ringer's or hetastarch/lactated Ringer's, with use of esophageal Doppler for guidance, in laparoscopic colectomy with an enhanced recovery protocol. A double-blinded, prospective, randomized, three-armed study with Institutional Review Board approval was used for patients undergoing laparoscopic segmental colectomy assigned to the standard, goal-directed/lactated Ringer's and goal-directed/hetastarch groups. A standard anesthesia and basal fluid administration protocol was used in addition to the goal-directed strategies guided by esophageal Doppler. Sixty-four patients undergoing laparoscopic colectomy (22 standard, 21 goal-directed/lactated Ringer's, 21 goal-directed/hetastarch) had similar operative times (standard, 2.3 hours; goal-directed/lactated Ringer's, 2.5 hours; goal-directed/hetastarch, 2.3 hours). The lactated Ringer's group received the greatest amount of total and milliliters per kilogram per hour of operative fluid (standard, 2,850/18; goal-directed/lactated Ringer's, 3,800/23; and goal-directed/hetastarch, 3,300/17; P < 0.05). The hetastarch group had the longest stay (standard, 64.9 hours; goal-directed/lactated Ringer's, 71.8 hours; goal-directed/hetastarch, 75.5 hours; P < 0.05). The standard group received the greatest amount of fluid during hospitalization (standard, 2.5 ml/kg/h; goal-directed/lactated Ringer's, 1.9 ml/kg/h; goal-directed/hetastarch, 2.1 ml/kg/h; P < 0.05). There was one instance of operative mortality in the goal-directed/hetastarch group. Goal-directed fluid management with a colloid/balanced salt solution offers no advantage and is more costly. However, goal-directed, individualized intraoperative fluid management with crystalloid should be evaluated further as a component of enhanced recovery protocols following colectomy because of reduced overall fluid administration.

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.

Effects of hemodilution with a hemoglobin-based oxygen carrier (HBOC-201) on ischemia/reperfusion injury in a model of partial warm liver ischemia of the rat

Background Ischemia/reperfusion injury is an unavoidable complication in liver surgery and transplantation. Hemodilution with colloids can reduce postischemic injury but limits oxygen transport. Hemoglobin-based oxygen carriers have been evaluated as blood substitute and provide a plasma-derived oxygen transport. It was the aim of our study to evaluate the combined benefits of hemodilution with a better oxygen supply to reperfused liver tissue by the use of HBOC-201 (Hemopure ®). Material and methods A model of partial warm liver ischemia in the rat was used. One group served as untreated control, the other groups were hemodiluted either with Ringer’s lactate, Dextran-70, HBOC-201 or a mixture of Dextran and HBOC-201. After reperfusion, intravital microscopy studies were done and tissue pO 2 levels and transaminases measured. Statistical analysis was done by one- and two-way ANOVA, followed by pairwise comparison. Results Hemodilution with Ringer’s lactate did not show any improvement compared to the control group. Dextran and HBOC group were superior to the Ringer and control animals in all parameters studied. Leucocyte adherence in postsinusoidal venules improved from 569.03 ± 171.87 and 364.52 ± 167.32 in control and Ringer group to 131.68 ± 58.34 and 68.44 ± 20.31/mm 2 endothelium in Dextran and HBOC group ( p < 0.001). Concerning tissue pO 2 levels, HBOC (23.4 ± 5.0 mmHg) proved to be superior to Dextran (7.9 ± 4.4 mmHg; p = 0.007). Conclusion HBOC was equivalent to Dextran in reducing I/R injury in the liver, but improved oxygenation of postreperfusion liver tissue.

Effect of fluid resuscitation for hemorrhagic shock on oxygenation of subjects in early period of first visit of high altitude area, an experimentation on dogs

To investigate the effect of fluid resuscitation on oxygenation of subjects with hemorrhagic shock in early period of first visit to area of high altitude, an experiment in dogs was performed. A model of serious hemorrhagic shock was reproduced by exsanguination resulting in a lowering of mean arterial pressure to (35+/-5) mm Hg (1 mm Hg=0.133 kPa) maintain for 1 hour. Thirteen mongrel dogs were carried to an area of 3,780 metres above sea level from an area of 1,510 metres, and they were randomly divided into three groups, namely lactated Ringer's (LR) group, 6% hydroxyethyl starch (HES) group, and control group. The dogs in LR group were infused intravenously LR in 1.5 times the volume of blood loss; those in 6% HES group were given HES in equal volume. No fluid infusion was given in the control group. After 1 hour of resuscitation, LR was intravenously given at 5 ml.kg(-1).h(-1) in all groups as maintenance dose. The changes in oxygenation were observed. All animals in control group were dead after 2 hours. One hour after establishment of shock, the oxygen consumption (VO(2)), oxygen delivery (DO(2)), oxygen extraction ratio (O(2)ER), arterial oxygen saturation (SaO(2)) in two resuscitation groups were significantly lower than those before shock, but venous oxygen saturation (Sv(2)) and alveolar-arterial oxygen difference (A-aDO(2)) were significantly higher (all P<0.05). In LR group, the oxygenation parameters including VO(2), DO(2), O(2)ER, SaO(2) after 2 hours of resuscitation were significantly higher than those 1 hour after shock, while A-aDO(2) was significantly lower (all P<0.05); and in HES group, VO(2), DO(2), O(2)ER were significantly higher than those 1 hour after shock, while SvO(2) was significantly lower (all P<0.05). All dogs with serious hemorrhagic shock would die of hemorrhagic shock in the early period of entering a high altitude area if fluid resuscitation is denied. Two hours after infusion of LR in 1.5 times of quantity of blood loss, oxygenation can be restored to expected normal values. Infusion of 6% HES with an equal volume of blood loss, oxygenation dose not reach expected level 2 hours after resuscitation.

The Effect of Trendelenburg Position, Lactated Ringer’s Solution and 6% Hydroxyethyl Starch Solution on Cardiac Output After Spinal Anesthesia

The aim of our study was to evaluate the effects of Trendelenburg position, infusion of 6% hydroxyetyl starch solution or lactated Ringer's solution on changes in cardiac output (CO) after spinal anesthesia in patients older than 50 yr. Seventy patients scheduled for lower extremity orthopedic surgery under spinal anesthesia were allocated randomly to one of the three treatment groups. In the Trendelenburg group, the patients were placed in the Trendelenburg position immediately after the spinal block for 10 min. In the hydroxyethyl starch group and the lactated Ringer's group, the patients received an infusion of 500 mL of 6% hydroxyethyl starch solution or 1000 mL of lactated Ringer's solution over 20 min after the spinal block. CO was measured continuously from 15 min before until 30 min after spinal anesthesia using the impedance cardiography method and arterial blood pressure with an automated device. P < 0.05 was considered statistically significant. The differences among treatment groups in CO were not statistically significant. Differences in the CO changes from baseline over time were significant. In the Trendelenburg group, CO did not change while the patient was in the Trendelenburg position. In the hydroxyethyl starch group, CO increased significantly after the block and remained significantly increased until the end of measurements. In the lactated Ringer's group, CO increased significantly 10 and 20 min after the block but, after stopping the infusion, CO started to decrease. Our study demonstrated that a decrease in CO after spinal anesthesia is prevented by placing the patient in the Trendelenburg position, or infusion of either lactated Ringer's solution or 6% hydroxyetyl starch solution. Although the effects of the infusion of the lactated Ringer's solution are transient, the effects of the infusion of 6% hydroxyethyl starch solution are extended beyond the time the infusion.

Hemoglobin-Based Oxygen Carrier and Altitude Performance in the Rat Model

Hemoglobin-based oxygen carriers (HBOC) may enhance oxygen carrying capacity of blood and potentially improve human performance at altitude. Oxygen delivery to exercising muscle may be enhanced with HBOC. PURPOSE: To determine, in the exercising rat model, if HBOC at altitude would increase exercise performance; and to investigate underlying hemodynamic determinants of oxygen delivery. METHODS: Study One: conscious male Sprague-Dawley rats rats were habituated to run on a treadmill for 4 days. On the study day, rats were randomly assigned to receive either a lactated Ringer's solution or an HBOC (Oxyglobin™, Biopure) via tail vein infusion. Rats were placed in a hypobaric chamber and the barometric pressure reduced to the equivalent of 13,500 ft (4,115 m) for a minimum of 20 min before running to exhaustion on the treadmill. Study Two: rats were acutely instrumented under anesthetic for BP, pulmonary artery pressure, and cardiac output (dye dilution). Animals were randomly assigned to a lactated Ringer's or HBOC group and infused via venous catheter. Following baseline measurements, conscious animals were exposed to either normoxia (FIO2 = 21 %) or hypoxia (FIO2 = 10%) for 4 hrs, with measurements at 2 and 4 hrs. RESULTS: Study One: rats running at altitude infused with lactated Ringer's averaged [mean (SEM)] 604 (142) sec vs. 307 (51) sec for HBOC treated (p=0.03, one-sided t-test). Study Two: HBOC animals both during normoxia and hypoxia had elevated arterial and pulmonary artery pressures, reduced cardiac output and decreased oxygen delivery (cardiac output times arterial oxygen content) [all p<0.05]. Cardiac output (ml/kg) was reduced from 224 (26) to 124 (14) at 4 hrs in normoxia, and from 242 (26) to 130 (12) in hypoxia. This corresponded to decreased oxygen delivery (ml O2/min/kg) from 40 (5) to 22 (2.5) in normoxia and from 23 (2.5) to 15.7 (1.6) in hypoxia, at 4 hrs. CONCLUSIONS: These studies suggest that HBOC reduces exercise performance at altitude because of its negative impact on cardiovascular function and oxygen delivery, despite increasing oxygen content. HBOC may alter cardiovascular function as a result of NO scavenging by the plasma borne hemoglobin (HBOC). Supported by the Defense Advanced Research Projects Agency (DARPA) and the Army Research Office (ARO) contract number W911NF-06-1-0318.

Effects of colloid and crystalloid solutions on endogenous activation of fibrinolysis and resistance of polymerized fibrin to recombinant tissue plasminogen activator added ex vivo

The study was conducted to explore the effects of colloid and crystalloid solutions on activation of fibrinolysis during orthopaedic surgery and to determine whether fluids facilitate clot dissolution at a particular fibrinolytic activity. Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured in plasma samples of 66 orthopaedic patients randomly receiving gelatin solution, hydroxyethyl starch (HES) (130/0.4), or exclusively Ringer's lactate solution. Plasma obtained before induction of anaesthesia (undiluted) and at the end of surgery (diluted) was exposed to recombinant tissue plasminogen activator (r-tPA) in vitro and analysed by modified thrombelastography (ROTEM). There were similar changes in t-PA and PAI-1 concentrations in the gelatin, HES, and Ringer's lactate groups. When compared with the effect of r-tPA on undiluted plasma samples, the presence of colloids prompted faster clot dissolution than did Ringer's lactate solution. Lysis index at 30 min decreased significantly [median (min/max); P vs Ringer's lactate solution] to 43 (1/82)% (P=0.007), 14 (3/70)% (P<0.001), and 91 (34/97)%, lysis onset time decreased to 1269 (1054/1743) s (P=0.007), 972 (490/1565) s (P<0.001), and 1970 (1260/2165) s, and lysis time to 2469 (1586/3303) s (P=0.019), 2002 (1569/3600) s (P=0.006), and 3012 (2017/3600) s in the gelatin, HES, and Ringer's lactate groups, respectively. The type of i.v. fluid used does not influence endogenously occurring fibrinolytic activity in patients undergoing major orthopaedic surgery. However, during hyperfibrinolysis, the presence of HES or gelatin solution facilitates clot disintegration to a greater extent than Ringer's lactate solution, because the weaker clots formed with colloids dissolve faster.

Hearing loss after spinal anesthesia: The effect of different infusion solutions

We speculate that the preoperative volume replacement with a convenient solution may protect the inner ear function after spinal anesthesia. The patients were randomized in a single-blind fashion into two groups: group LR (n = 40) received lactated Ringer's and group GF (n = 40) received gelatin polysuccinate 4% (Gelofusine). Spinal anesthesia was performed with a 25 G Quincke needle and was given bupivacaine 0.5% 10 mg and fentanyl 25 microg. Audiograms were performed preoperatively and 2 days postoperatively. The overall incidence of hearing loss was 7.5%. The hearing loss was unilateral in two and bilateral in four patients. Hearing loss occurred within the low-frequency range and the hearing thresholds returned to normal by the fifth postoperative day. Although the incidence of hearing loss for the lactated Ringer's group was higher than the Gelofusine group, there was no statistically significant difference between the groups. For medicolegal and ethical reasons, patients should be informed about the possibility of hearing loss after spinal anesthesia.

Intrapartum maternal glucose infusion and fetal acid–base status

Objective To compare the effects of an intrapartum infusion of a lactated Ringer solution or a glucose-boosted saline solution on the acid–base status of umbilical arterial blood. Method In a prospective clinical trial 178 women in labor were randomized to receive intravenously either a lactated Ringer solution or a saline solution boosted with 5% glucose. Umbilical arterial blood was then assessed for acid–base status. Results There were significant differences between the lactated Ringer group and the glucose group in umbilical artery pH values (7.25 ± 0.07 vs. 7.28 ±0.06; P = 0.008), pCO 2 values (44.8 ± 5.6 mm Hg vs. 41.6 ± 4.1 mm Hg; P = 0.001), and base excess (− 7.3 ± 2.1 mEq/L vs. − 6.6 ± 1.8 mEq/L; P = 0.02). Conclusion Intrapartum intravenous fluid containing a 5% glucose solution reduces umbilical cord acidemia and hypercarbia.

Hypertonic hydroxyethyl starch solution for hypovolaemia correction following heart surgery

The aim of the study was to evaluate the effect of hypertonic NaCl hydroxyethyl starch solution on haemodynamics and cardiovascular parameters in the early postoperative period in patients for correction of hypovolaemia after heart surgery. Eighty patients undergoing myocardial revascularisation at the Clinic of Cardiac Surgery of the Heart Centre (Kaunas University of Medicine) were randomly divided into two groups. The HyperHaes group (n = 40) received 250ml 7.2% NaCl/6% HES solution and the control Ringer's acetate group (n = 40) received placebo (500 ml Ringer's acetate solution) for volume correction after the surgery. After infusion of HyperHaes solution, cardiac index increased from 2.69 (0.7) to 3.52 (0.8) l/min/m2, systemic vascular resistance index, pulmonary vascular resistance index and the gradient between central and peripheral temperature decreased, and oxygen transport parameters improved. Ringer's group patients needed more intensive infusion therapy (4050.0 (1102.2) ml in the Ringer's group, 3513.7(762.5) ml in the HyperHaes group). During the first 24 hours postoperatively, diuresis was significantly higher in the HyperHaes group (3640.0 (1122.9) ml and 2736.0 (900.7) ml), total fluid balance was lower in HyperHaes group (1405.6 (1519.0) ml and 2718.3 (1508.0)ml, respectively). After the infusion of HyperHaes solution, no adverse events were noted. HyperHaes solution had a positive effect on haemodynamic parameters and microcirculation. Oxygen transport was more effective after HyperHaes solution infusion. Higher diuresis, lower need for the infusion therapy for the first 24 hours and lower total fluid balance were determined in the HyperHaes group. No adverse effects were observed after HyperHaes solution infusion.

Hydroxyethyl starch is superior to lactated Ringer as a replacement fluid in a pig model of acute normovolaemic haemodilution

Tissue tolerance to oxygen privation during acute normovolaemic haemodilution with different fluids remains unclear. We tested the hypothesis that hydroxyethyl starch (HES) is superior to lactated Ringer's solution in pigs for preserving tissue perfusion during acute normovolaemic haemodilution. Twenty-four animals were randomized into control, lactated Ringer's solution and HES groups. All groups, except the control, underwent acute normovolaemic haemodilution. Haemodynamics, oxygen parameter indices, global anaerobic metabolic markers, echocardiographic parameters, gastric tonometry and serum osmolarity were monitored at baseline, immediately after (0 min) and 60 and 120 min after the end of haemodilution. Myocardial, liver, stomach and intestine samples were collected for further evaluation. Cardiac and oxygen parameter index responses to acute normovolaemic haemodilution were comparable. However, the increment in cardiac index, stroke volume index, and left ventricular stroke work index were more sustained in the starch group. In the lactated Ringer's group, gastric pH decreased significantly and was accompanied by a significant increase in lactate. Myocardial ultrastructure was better preserved in the starch group. The other tissue samples presented no change. In this model of ANH, the starch group had a superior haemodynamic response. Minor loss of myocardial cellular integrity and preserved gastric pHi reinforce these findings.

Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats

Background This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. Methods The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. Results At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. Conclusions As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.

Fluid preload before spinal anaesthesia in Caesarean section

We evaluated the effect of two different preload solutions: (i) Ringer's lactate (compound sodium lactate intravenous infusion BP) and (ii) 0.9% sodium chloride solution on the neonatal acid-base status of the newborn infants. The two standard regimens were compared to detect a possible difference. A 2 L crystalloid fluid bolus was administered immediately before spinal anaesthesia for elective Caesarean section in two groups of 20 healthy parturients, while rigorously maintaining maternal normotension. No significant differences in the Apgar scores at 1 and 5 min, or infant well-being were demonstrated in either of the two groups. The data show that umbilical artery PCO2 is lower in the Ringer's lactate group and that pH is insignificantly higher by 0.03. The choice of Ringer's lactate or saline for fluid preload does not have any effect on neonatal well-being.

Hypertonic Lactated Saline Resuscitation Reduces the Risk of Abdominal Compartment Syndrome in Severely Burned Patients

Secondary abdominal compartment syndrome is a lethal complication after resuscitation from burn shock. Hypertonic lactated saline (HLS) infusion reduces early fluid requirements in burn shock, but the effects of HLS on intraabdominal pressure have not been clarified. Patients admitted to our burn unit between 2002 and 2004 with burns > or =40% of the total body surface area without severe inhalation injury were entered into a fluid resuscitation protocol using HLS (n = 14) or lactated Ringer's solution (n = 22). Urine output was monitored hourly with a goal of 0.5 to 1.0 mL/kg per hour. Hemodynamic parameters, blood gas analysis, intrabladder pressure as an indicator of intraabdominal pressure (IAP), and the peak inspiratory pressure were recorded. Pulmonary compliance and the abdominal perfusion pressure were also calculated. In the HLS group, the amount of intravenous fluid volume needed to maintain adequate urine output was less at 3.1 +/- 0.9 versus 5.2 +/- 1.2 mL/24 h per kg per percentage of total body surface area, and the peak IAP and peak inspiratory pressure at 24 hours after injury were significantly lower than those in the lactated Ringer's group. Two of 14 patients (14%) in the HLS group and 11 of 22 patients (50%) developed IAH within 20.8 +/- 7.2 hours after injury. In patients with severe burn injury, a large intravenous fluid volume decreases abdominal perfusion during the resuscitative period because of increased IAP. Our data suggest that HLS resuscitation could reduce the risk of secondary abdominal compartment syndrome with lower fluid load in burn shock patients.

Hepatic Apoptosis after Hemorrhagic Shock in Rats Can Be Reduced Through Modifications of Conventional Ringer’s Solution

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. 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. 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. 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.

EFFECT OF THE BOVINE HEMOGLOBIN SOLUTION (HBOC-301) WITH AND WITHOUT ISOVOLEMIC HEMODILUTION ON PANCREATIC TISSUE OXYGENATION, PANCREATIC MICROCIRCULATION AND SURVIVAL IN PIGS WITH SEVERE ACUTE PANCREATITIS

Background: Disturbed microcirculation and as a consequence decreased tissue oxygenation is a crucial effect in the cascade from the self limiting mild edematous to the often fatal form of acute hemorrhagic necrotizing pancreatitis.The aim of this study was to evaluate the therapeutic approach of volume therapy with HBOC-301 with and without IHD with regard to pancreatic tissue oxygenation, pancreatic microcirculation and survival in pigs suffering from acute necrotizing pancreatitis. Methods: After approval of the local ethics committee 39 pigs were anesthetized, endotracheally intubated and normoventilated (FIO2:0.3). After laparotomy and splenectomy the pancreatic duct was canulated. Pancreatic tissue oxygen tensions (tpO2) were measured using a silicon catheter (Licox Medical Systems, Germany). Pancreatic microcirculation was assessed by a laser-doppler perfusion imager (Perimed, Sweden). After 30 min. equilibration (M0) AP was induced by a combination of intravenous cerulein and intraductal glycodeoxycholic acid. Fifteen min. and 75 min. after induction of AP animals were randomized to isovolemic (PAOP-constant) hemodilution with 10% HES 200,000/0.5 plus HBOC-301 (+0.6 g dl-1 plasmatic Hb; Oxyglobin®, Biopure, USA) (IHD+HBOC) or to HBOC-301 (+0.6 g dl-1 plasmatic Hb) (HBOC), or to hemodilution with Ringer's solution (IHD RINGER) to a hematocrit (Hct) of 15%. TpO2 and microcirculation were measured every hour. After six hours catheters were removed, the abdomen was closed and animals were extubated. After six days (144 hours) surviving animals were sacrified. Statistical analyses were performed using the Kolmogorov-Smirnov test for normal distribution, Kruskal-Wallis test for group differences, Student`s t-test for normally distributed data and Chi-square test for the survival rate (significance p < 0.05). Results: After induction of AP tpO2 decreased in all groups and increased significantly to normal levels after application of HBOC-301 with and without IHD compared to the IHD RINGER-group. The survival rate at the end of the observation period was higher in the IHD+HBOC group (10/13) (p < 0.001) and in the HBOC-group (9/13) (p < 0.001) compared to the Ringer group (2/13) (p = 0,001 Kruskal-Wallis Test). The extend of the microcirculatory impairment corresponded with these results. Conclusion: The therapeutic application of HBOC-301 was able to normalize pancreatic tissue oxygen and improve survival after induction of severe AP. The IHD had no additional effect.

Pharmacological study of BRS, a new bicarbonated Ringer's solution, in haemorrhagic shock dogs

Sodium bicarbonate is the most physiological alkalinizing agent. The effect of a new bicarbonated Ringer's solution (BRS) containing Mg2+, on metabolic acidosis and serum magnesium abnormality were evaluated and compared with those of acetated Ringer's (ARS), lactated Ringer's (LRS) and Ringer's (RS) solutions in an experimental haemorrhagic shock model with dogs. Animals were randomly divided into six groups (n = 6 in each group), a sham-operated group, an operated group without infusion, and 4 operated groups with infusion (BRS, ARS, LRS and RS groups). Each RS was intravenously administered at 60 mL kg(-1) h(-1) for 1.5 h. Arterial blood gases, plasma electrolytes and cardiovascular parameters were analysed. BRS significantly improved blood base excess values, which were decreased by blood-letting, faster and more markedly than did LRS and RS (BRS--6.3 +/- 0.5 mEq L(-1); LRS--9.2 +/- 1.1 mEq L(-1); RS--12.4 +/- 1.0 mEq L(-1) at the end of infusion). The alkalinizing effect of BRS tended to be better than that of ARS but not significantly so. The serum Mg2+ concentration was well-maintained by BRS as compared to other RS (BRS 1.5 +/- 0.0 mgdL(-1); ARS 1.2 +/- 0.0mgdL(-1); LRS 1.1 +/- 0.0mgdL(-1); RS 1.3 +/- 0.1 mgdL(-1), at the end of infusion). These results suggest that BRS is a suitable perioperative solution for metabolic acidosis and serum electrolyte balance among RS tested.

Changes in acid-base balance following bolus infusion of 20% albumin solution in humans

To evaluate changes in acid-base balance following bolus infusions of a 20% albumin solution. Randomized prospective study in a university hospital. Two groups of eight patients each undergoing gynecological surgery. Patients were randomly assigned to receive either 0.9% saline or lactated Ringer's solution. At the end of surgery two boluses of 0.5 g/kg body weight of a 20% albumin solution were administered. Arterial blood gases, electrolytes, and total protein were measured. The strong ion difference and the amount of weak plasma acid were calculated. pH and titratable acidity of the 20% albumin solution were determined. The infusion of a 20% albumin solution resulted in a significant decrease in pH from 7.284 to 7.262 in the saline group and from 7.422 to 7.394 in the Ringer's group. In both groups the 20% albumin solution caused an increase in strong ion difference and an increase in the amount of weak plasma acid. The observed changes in serum bicarbonate concentration were in good agreement with the changes in strong ion difference and the amount of weak plasma acid. The 20% albumin solution possessed a pH of 6.95 and a titratable acidity of 8.5 [corrected] mEq/l. According to the Stewart approach, the observed changes in acid-base balance are the net result of the two opposing effects of the strong ion difference and the amount of weak plasma acid. Alternatively, the acidifying effect of the 20% albumin solution may stem from the titratable acid content of the solution.