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.     

Hypertonic saline in the traumatic hypovolemic shock: meta-analysis

Background

A wealth of evidence from animal experiments has indicated that hypertonic saline (HS) maybe a better choice for fluid resuscitation in traumatic hypovolemic shock in comparison with conventional isotonic saline. However, the results of several clinical trials raised controversies on the superiority of fluid resuscitation with HS. This meta-analysis was performed to better understand the efficacy of HS in patients with traumatic hypovolemic shock comparing with isotonic saline.

Materials and methods

According to the search strategy, we searched the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, which was completed on October 2013. After literature searching, two investigators independently performed the literature screening, assessment of quality of the included trials, and data extraction. Disagreements were resolved by consensus or by a third investigator if needed. The outcomes included mortality, blood pressure, fluid requirement, and serum sodium.

Results

Six randomized controlled trials were included in the meta-analysis. The pooled risk ratio for mortality at discharge was 0.96 (95% confidence interval [CI], 0.82–1.14), whereas the pooled mean difference for the change in systolic blood pressure from baseline and the level of serum sodium after infusion was 6.47 (95% CI, 1.31–11.63) and 7.94 (95% CI, 7.38–8.51), respectively. Current data were insufficient to evaluate the effect of HS on the fluid requirement for the resuscitation.

Conclusions

The present meta-analysis was unable to demonstrate a clinically important improvement in mortality after the HS administration. Moreover, we observed HS administration maybe accompanied with significant increase in blood pressure and serum sodium.     

高渗/高胶液与休克复苏

临床中通常使用等渗晶体、胶体或成份血作为休克复苏液 ,但鉴于这些液体在复苏中的不力表现 ,寻找一种全新的复苏液成为当务之急。近年来高渗 /高胶液在临床应用中以取得满意效果并展现出良好前景。笔者就高渗 /高胶液复苏机制 ,对机体的影响及使用中的问题做一综述。     

Hypertonic saline prevents early bacterial translocation in hemorrhagic shock

The most appropriate solution for volume replacement in hemorrhagic shock is controversial; however, hypertonic saline (HTS) solutions have recently gained widespread acceptance. In this study, various solutions were used to resuscitate rats in hemorrhagic shock, and their impact on the extent of bacterial translocation was investigated. Rats were bled to a mean arterial blood pressure of about 35 mmHg which was maintained for 30 min. They were then randomized into six groups. Blood pressure was found to be regulated by blood + lactated Ringer's solution (LR) and HTS+LR, but no significant improvement was observed in the control and LR groups. Groups II (7.5% HTS+60 ml/kg LR) and IV (60 ml/kg LR + autologous blood) had a significantly better result than groups I (7.5% HTS), III (60 ml/kg LR), and IV (P<0.05), among which no statistically different results were seen (P>0.05). While no organisms were isolated from the mesenteric lymph nodes in the sham group, the rates of positive culture were 12.5%, 12.5%, 50%, 62.5%, and 62.5% in groups I, II, III, and the control group, respectively.Escherichia coli was the most commonly isolated organism. HTS+LR was demonstrated to be effective for decreasing the rate of early bacterial translocation to mesenteric lymph nodes and also for restoring the mean arterial pressure.     

Hypertonic saline solution-hetastarch for fluid resuscitation in experimental septic shock

Hypertonic colloid solutions have been found efficacious in the resuscitation from hemorrhagic/traumatic shock. The present study investigated the hemodynamic, gasometric, and metabolic effects of hypertonic colloids in endotoxic shock in the dog. Thirty minutes after administration of 3 mg/kg normal body weight of Escherichia coli endotoxin, dogs were randomly assigned to receive 10 mL/kg hydroxyethylstarch (HES) either in 0.9% NaCl (HES, 10 dogs) or in 7.5% NaCl (HT-HES, 10 dogs) in 30 min. Thereafter, 0.9% NaCl solution was administered in volumes adequate to maintain pulmonary artery balloon-occluded pressure at baseline levels. Total fluid administered averaged 64 +/- 30 mL/kg (mean +/- SD) in the HES group and 73 +/- 34 mL/kg in the HT-HES group. As these differences were not statistically significant, total sodium load was higher in the HT-HES group. The persistent volume effect was associated with persistently lower hematocrit and protein levels in the HT-HES group. Initial fluid resuscitation with HT-HES resulted in arterial pressure, cardiac filling pressures, cardiac output, stroke volume, and rates of oxygen delivery and oxygen consumption that were greater than those with HES. Vascular resistances were similar. Analysis of left ventricular function curves also indicated an improvement in cardiac performance. However, these effects almost completely vanished during the remainder of the study. In the HT-HES group, serum sodium and osmolality levels increased to 167 +/- 4 mEq/L and 344 +/- 4 mOsm/kg H2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertonic saline resuscitation in a porcine model of severe hemorrhagic shock

The purpose of this study was to investigate the effect of 7.5% hypertonic saline solution (HTS) as the initial solution in resuscitation of a pig in shock. Twenty-two animals were bled 50% of their blood volume over 30 minutes and maintained in shock for 60 minutes. The 14 survivors were divided into two groups. The first group was given 20 mL/kg of lactated Ringer's solution (LR) over a ten-minute period, while the second group was given 10 mL/kg of HTS. Both groups were then given LR at 2 mL/kg/min until the mean arterial pressure reached 80 mm Hg. The HTS group achieved a more rapid rise in mean arterial pressure over the first ten minutes of resuscitation. During this period, the cardiac index increased significantly more in the HTS group when compared with the LR group. All animals in the HTS group developed an adequate urine output. Only two animals in the LR group developed an adequate urine output. Hypertonic saline solution markedly improved survival, and there were significant improvements in hemodynamics. This was accomplished with smaller volumes of resuscitation fluid and may prove useful under conditions where intravascular access is limited.     

Hypertonic saline in hydatid disease

The objective of this study was to determine the scolicidal effects of saline in different concentrations using different exposure times and to examine whether hypertonic saline can be used to irrigate the abdomen when there is a free intraperitoneal perforation of hydatid disease. Various concentrations of saline solutions (0.09%, 3.0%, 6.5%, 10%, 15%, 20%, 25%, 30%) were added to concentrated echinococcus granulosus sediments for the following times: 1, 2, 3, 4, 5, 10, 15, 30, 45, and 60 minutes. Normal (0.09%), 3.0%, and 6.5% saline resulted in high viability ratios after 60 minutes' exposure. Complete lethality for 10%, 15%, 20%, 25%, and 30% saline occurred at the end of 75, 10, 6, 3, and 3 minutes, respectively. During the second part of the study, 20 Sprague-Dawley rats were used for abdominal saline irrigation in four groups: 30% NaCl for 3 minutes; 20% NaCl for 6 minutes; intravenous isotonic dextrose water and furosemide plus 30% NaCl irrigation for 3 minutes; the same prophylactic therapy plus 20% NaCl irrigation for 6 minutes. Sodium and chloride values rose significantly (20–30%) shortly after hypertonic saline irrigation in each group (p < 0.01). Support with isotonic dextrose and furosemide before irrigation did not have any beneficial effect on biochemical values or mortality. The 24- and 48-hour mortality rates were 70% and 90%, respectively. These studies illustrate that the scolicidal effect of hypertonic saline is limited in low concentrations, but an increase in the concentration can augment its adverse effects. Peritoneal irrigation with hypertonic saline should be avoided for intraabdominal perforated hydatid disease. Therefore, we concluded that hypertonic saline is not a good scolicidal agent to prevent recurrence of hydatid disease.     

Hypertonic/hyperoncotic fluid resuscitation after hemorrhagic shock in dogs.

We compared canine systemic and cerebral hemodynamics after resuscitation from hemorrhagic shock with 4 mL/kg (a volume approximating 12% of shed blood volume) of 7.2% saline (HS; 1233 mEq/L sodium), 20% hydroxyethyl starch (HES) in 0.8% saline, or a combination fluid consisting of 20% hydroxyethyl starch in 7.2% saline (HS/HES). Eighteen endotracheally intubated mongrel dogs (18-24 kg) were ventilated to maintain normocarbia with 0.5% halothane in nitrous oxide and oxygen (60:40). After a 30-min period of hemorrhagic shock (mean arterial blood pressure = 40 mm Hg), extending from time T0 to T30, animals received one of three randomly assigned intravenous resuscitation fluids: HS, HES, or HS/HES. Data were collected at baseline, at the beginning and end of the shock period (T0 and T30), immediately after fluid infusion (T35), and at 60-min intervals for 2 h (T95, T155). After resuscitation, mean arterial blood pressure and cardiac output increased similarly in all groups, but failed to return to baseline. Intracranial pressure decreased during shock and increased slightly, immediately after resuscitation in all groups. During shock, cerebral blood flow (cerebral venous outflow method) declined in all groups. After resuscitation, cerebral blood flow increased, exceeding baseline in the HS and HS/HES groups but remaining low in the HES group (P less than 0.05 HS vs HES at T35). We conclude that small-volume resuscitation (4 mL/kg) with HS, HS/HES, or HES does not effectively restore or sustain systemic hemodynamics in hemorrhaged dogs. In dogs without intracranial pathology, the effects on cerebral hemodynamics are also comparable, except for transiently greater cerebral blood flow in the HS group in comparison with the HES group.     

The effect of imidazole in endotoxin shock in dogs

The effect of imidazole, a thromboxane A2 inhibitor, in endotoxin shock in dogs was studied. Thromboxane A2 is a vasoconstrictor and enhances platelet and neutrophil aggregation. The purpose of this study was to examine the hemodynamic modifications of endotoxin shock with imidazole. Thirty dogs were studied, all receiving 1 X 10(8) live Escherichia coli/kg over a 30-minute period. The dogs were divided into three groups of ten dogs each. The first group received no treatment. The second group received a concomitant infusion of imidazole 25 mg/kg per hour. In a third group the imidazole infusion was delayed for 1 hour after the E. coli infusion. Mean arterial pressure (MAP), pulmonary wedge pressure (PWP), central venous pressure (CVP), cardiac output (CO), and systemic vascular resistance (SVR) were measured at 30-minute intervals. Hemoglobin (HGB), white blood count (WBC), a-A gradient (a-A grad), A-V 02 difference (AV02 diff), and fluid requirements were measured at 60-minute intervals. The endotoxin shock response in untreated control dogs was characterized by significant changes over time in MAP and SVR (decreased), and CO and a-A grad (increased). The imidazole group was significantly different, as the MAP and SVR did not decrease and the CO did not increase as in the control group. The control group required significantly more fluids than the imidazole group, while the HGB remained stable suggesting more capillary permeability in the control group. The delayed treatment group was statistically similar to the control animals. These data suggest that imidazole significantly modifies the hemodynamic response to endotoxin shock and may reduce the associated capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS)     

高渗盐复合液用于颅脑外伤合并失血性休克的治疗

目的研究高渗盐溶液（7．5％氯化钠／6％右旋糖酐液,HSD）及高渗盐复合液（高渗氯化钠／羟乙基淀粉40注射液,霍姆）用于颅脑外伤合并失血性休克患者的治疗效果。方法将93名颅脑外伤合并失血性休克的患者随机分为2组,为霍姆组（HH组）和HSD组,分别使用霍姆和HSD进行液体复苏,于To（入院时）、15分钟（L）、30分钟（B）、60分钟（B）不同时间点监测记录平均动脉压（MAP）、心率（HR）、尿量（VOL）变化;监测人院时及输液60分钟后的血红蛋白（Hb）、红细胞压积（HCT）、GCS评分;记录早期复苏时间、术前总输液量、胶体液比例;记录入院后24小时死亡率、1周死亡率。结果输液后30分钟、60分钟,HH组的平均动脉压显著大于HsD组（P≮O．05）。输液60分钟,HH组的心率显著小于HSD组（P〈0．05）。在15分钟、30分钟、60分钟,HH组的尿量显著多于HSD组（P〈0．05）。HH组患者60分钟后测得HCT与Hb均较人院时有显著下降（P〈0．05）。HSD组60分钟后的HCT与入院时无显著性差异（P〉O．05）,而输液60分钟后的Hb显著低于入院前（P〈O．05）。GCS评分,HH组液体复苏前后有显著性差异（P〈O．05）,而HSD组前后却没有显著差异。液体复苏60分钟后的GCS值HH组显著大于HSD组（RO．05）。HH组手术前平均输液量显著少于HSD组fP〈0,05）。人院24小时内及1周内,HH纽死亡率均稍低于HSD组死亡率,但无显著差异（P〉O．05）。结论在颅脑外伤合并创伤失血性休克的情况下,补充高渗盐复合液不仅能更快的纠正组织低灌注,保护重要心、脑、肺等脏器,降低颅内压,还能减少输液量。     

高渗氯化钠羟乙基淀粉复合液对失血性休克肺的保护作用

目的观察用高渗氯化钠羟乙基淀粉复合液(7.5%氯化钠 6%羟乙基淀粉200/0.5,HHS)小容量复苏对失血性休克后肺损伤的影响。方法雄性SD大鼠随机分为五组:正常对照组(CON组,n=6):不放血不补液;其他大鼠通过放血使MAP降至45mmHg并维持120min,然后分为:休克组(SH组,n=6),不补液复苏;HHS组(n=8),用HHS5ml/kg静脉滴注;7.5%氯化钠高渗溶液组(HTS组,n=6),用7.5%NaCl5ml/kg静脉滴注;复方乳酸钠组(LR组,n=7),用3倍失血量的复方乳酸钠静脉滴注。观察休克2h末、补液结束即刻、15、30、60、120、180min时MAP、CVP的变化,测定补液结束2、24h存活动物的氧合指数和肺水含量、肺髓过氧化物酶(MPO)水平、肺损伤评分。结果在补液结束120、180min,HTS组MAP、CVP低于HHS和LR组(P<0.05);在补液结束24h,HHS组氧合指数、肺水含量、肺MPO水平、肺损伤评分优于HTS和LR组(P<0.05)。结论用HHS小容量复苏失血性休克,维持血流动力学稳定时间更长;对肺组织的保护作用优于7.5%氯化钠高渗溶液或复方乳酸钠。     

Hypertonic saline resuscitation improves intestinal microcirculation in a rat model of hemorrhagic shock

BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock (HS) often restores and maintains hemodynamics but fails to restore intestinal perfusion. Post-CR intestinal ischemia has been implicated in the initiation of a gut-derived exaggerated systemic inflammatory response and in the progressive organ failure following HS. We propose that intestinal ischemia can be prevented with hypertonic saline resuscitation (HTSR). METHODS: Anesthetized male Sprague-Dawley rats (200 to 215 g) were hemorrhaged to 50% of mean arterial pressure (MAP) for 60 minutes and randomly assigned to 1 of the resuscitation groups (n = 7 each): Group I: sham operation and no HS; Group II: HS + CR with the return of the shed blood + 2 volumes of normal saline (NS); Group III: HS + return of the shed blood + hypertonic saline (HTS); (7.5 % NaCl, 4 ml/kg); Group IV: HS + HTS, then return of the shed blood after 60 minutes; Group V: HS + HTS, then 1 volume of NS after 60 minutes. Microvascular diameters of inflow (A1) and proximal and distal premucosal arterioles (A3) in terminal ileum and flow in A1 were measured using in vivo videomicroscopy and optical Doppler velocimetry. Hematocrit, plasma osmolarity, and electrolytes were measured in Groups II and III. RESULTS: HS caused a selective vasoconstriction in A1 arterioles that was not seen in the premucosal arterioles. CR restored and maintained MAP and caused generalized, progressive vasoconstriction at all intestinal arteriolar levels that is associated with hypoperfusion. HTSR failed to restore or maintain MAP or intestinal A1 arteriolar blood flow until the shed blood was returned. However, HTSR prevented the post-resuscitation, premucosal vasoconstriction and produced an insidious selective vasodilation in the A3 arterioles, which was most significant with early blood return (Group III). This selective arteriolar vasoactivity was associated with a significant improvement of endothelial cell function. Plasma hyperosmolality and hypernatremia persisted during the entire 2 hours post-resuscitation with HTS. CONCLUSIONS: Small-volume HTSR can be used as a resuscitation regimen at the trauma scene and for selective clinical conditions where hypotensive resuscitation is indicated. HTSR improves intestinal perfusion by selective vasodilation of the precapillary arterioles even at MAP close to shock levels.     

Effects of ulinastatin on endotoxin shock in dogs]

The therapeutic effect of ulinastatin, an inhibitor of the protease activity, on endotoxin shock was evaluated using 17 Beagle dogs. Single intravenous injection of ulinastatin at a dose of 5,000 or 25,000 U.kg-1 failed to suppress the endotoxin-induced circulatory disturbance but significantly inhibited increases in pulmonary arterial pressure and pulmonary vascular resistance that occur early following administration of endotoxin. Elevation of PGI2, TXA2 and LTB4 by endotoxin shock was significantly inhibited by administration of 25,000 U.kg-1 of ulinastatin. Elevation of the granulocytic elastase activity was inhibited dose-dependently by administration of ulinastatin. The above results indicate that ulinastatin may be a promising drug for the treatment of endotoxin shock.     

Myocardial insulin resistance during acute endotoxin shock in dogs

Myocardial insulin responsiveness was determined in open-chest pentobarbital sodium-anesthetized dogs before and after endotoxin administration. Animals were instrumented to measure mean arterial blood pressure (MABP), heart rate (HR), and coronary blood flow. Myocardial glucose uptake and myocardial oxygen uptake (MVO2) were determined during a basal control period and after a hyperinsulinemic-euglycemic clamp procedure over a wide range of insulin concentrations. The clamp was accomplished by intravenously infusing insulin (0-4000 mU/min) and 20% glucose in sufficient amounts to maintain arterial glucose concentrations within 5 mg/dl of the control value. In a separate series of experiments, myocardial insulin responsiveness was determined by use of a single dose of insulin (4000 mU/min). This was done to determine whether antecedent insulin infusions during the sequential clamp procedure would affect the responsiveness of the heart. In control experiments, myocardial glucose uptake increased without any changes in HR, MVO2, or MABP. Maximum myocardial glucose uptake occurred at an insulin infusion rate between 400 and 4000 mU/min. A single concentration of insulin resulted in similar increases in myocardial glucose uptake as with the sequential clamp protocol. Acute endotoxin shock was induced by bolus injection of 1 mg/kg Salmonella typhimurium endotoxin (Difco Labs, Detroit, MI). One hour after administration of endotoxin, basal myocardial glucose uptake was decreased compared with the control animals. After 1 h of endotoxin shock, the heart was refractory to all concentrations of insulin, suggesting the site for altered insulin response was being mediated by a postreceptor mechanism.