Mild hypothermia prolongs the survival time during uncontrolled hemorrhagic shock in rats

OBJECTIVE: To test our hypothesis that during lethal uncontrolled hemorrhagic shock (UHS) in rats, mild hypothermia of either 36 or 34 degrees C would prolong the survival time in comparison with normotherma of 38 degrees C. METHODS: Twenty-four rats were lightly anesthetized with halothane and maintained spontaneous breathing. UHS was induced by blood withdrawal of 2.5 ml/100 g over 15 min, followed by 75% tail amputation. Immediately after the tail cut, the rats were randomly divided into three groups (eight rats for each); normothermic Group 1 (control, rectal temperature 38 degrees C), and mild hypothermic Groups 2 (36 degrees C) and 3 (34 degrees C). Hypothermia was induced and maintained by body surface cooling. The rats were then observed without fluid resuscitation until their death (apnea and no pulse) or for a period of 240 min maximum. RESULTS: The rectal temperature was cooled down to 36 and 34 degrees C in 5 and 10 min, respectively. The mean survival time, which was 76+/-26 min in the control group (38 degrees C), was nearly doubled by mild hypothermia, 178+/-65 min for Group 2 (36 degrees C) (P<0.01 vs. control) and 144+/-54 min for Group 3 (34 degrees C) (P<0.05 vs. control) (no significant difference between Group 2 and 3). Additional blood losses from tail stumps were not significantly different among the three groups. CONCLUSION: Mild hypothermia of either 36 or 34 degrees C prolongs the survival time during lethal UHS in rats.     

Combination of therapeutic mild hypothermia and delayed fluid resuscitation improved survival after uncontrolled haemorrhagic shock in mechanically ventilated rats

We challenged the current management of uncontrolled haemorrhagic shock (UHS) and put forward a hypothesis that therapeutic mild hypothermia combined with delayed fluid resuscitation will improve the survival rate. After an initial blood withdrawal of 3 ml/100g for 15 min, the rat's tail was amputated up to 75% to induce UHS phase I. The mean arterial blood pressure (MAP) was maintained at 40 mmHg or 80 mmHg, according to the assigned study group. This was followed by homeostasis of the tail wound and increase of the MAP up to 100 mmHg during resuscitation phase II. Finally, phase III was an observation of phase up to 72 h. Rats were anaesthetised and randomised into four groups. Group 1 received immediate fluid resuscitation and normothermia. Group 2 received immediate fluid resuscitation and therapeutic mild hypothermia. Group 3 received limited fluid solutions to maintain MAP at 40 mmHg and normothermia. Group 4 also received limited fluid solution, but the rats were subjected to therapeutic mild hypothermia. In groups 2 and 4, the body temperature was kept at 34 degrees C throughout the UHS phase I and resuscitation phase II. At the end of the observation phase III, the brains of the animals were fixed and analysed histologically. The blood loss from the tail during the UHS phase I was significantly higher in groups 1 and 2. The survival rate was 33.3, 83.3, 58.3 and 91.7%, respectively in groups 1-4. In all surviving rats, no histological brain damage was observed. These results indicate that therapeutic mild hypothermia or delayed fluid resuscitation increase the survival rate in this model. However, when mild hypothermia and limited fluid resuscitation were combined, the survival rate was the highest.     

Improved survival of hemorrhagic shock with oxygen and hypothermia in rats.

A previously established model in awake rats of hemorrhagic shock (HS) with 25% spontaneous survival rate (without resuscitation) was used to evaluate the effects of 4 novel life-supporting first aid (LSFA) measures on survival time and rate. After shed blood volume (SBV) of 3.25 ml/100 g, withdrawn over 20 min, hemodynamic and respiratory responses were recorded to 3 h and survival to 24 h. The 5 groups of 20 rats each (total n = 100) were as follows: group I, controls without treatment; II, oxygen 100% inhalation; III, external cooling to rectal temperature 30 degrees C; IV, Ringer's solution 5 ml/100 g rectally; and V, acoustic and surface stimuli for arousal. Survival rates were: control group I, 35% at 3 h and 15% at 24 h; oxygen group II, 75% (P less than 0.05 compared with group I) at 3 h and 60% (P less than 0.05 compared with group I) at 24 h; hypothermia group III, 65% at 3 h and 45% (P less than 0.05 compared with group I) at 24 h; rectal fluid group IV, 50% at 3 h and 40% at 24 h; stimulated group V, 15% at 3 h and 15% at 24 h. Compared with group I, median survival times during HS 0-3 h were longer in groups II and III; and self-resuscitation attempts were longer in groups II, III and IV. We conclude that in untreated severe hemorrhagic shock, chances of survival to delayed arrival of advanced life support with i.v. fluid resuscitation might be increased with O2 inhalation and/or moderate external cooling.     

Mild or moderate hypothermia, but not increased oxygen breathing, increases long-term survival after uncontrolled hemorrhagic shock in rats

OBJECTIVE: To test the hypotheses that, for uncontrolled hemorrhagic shock (UHS) in rats, mild hypothermia, compared with normothermia, would increase long-term survival as well as moderate hypothermia, oxygen breathing would increase survival further, and hypothermia and oxygen would mitigate visceral ischemia (dysoxia) during UHS. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory. SUBJECTS: A total of 54 male Sprague-Dawley rats. INTERVENTIONS: Under light anesthesia and spontaneous breathing, rats underwent UHS phase I of 75 mins, with initial withdrawal of 3 mL/100 g of blood over 15 mins, followed by UHS via tail amputation and limited fluid resuscitation to maintain mean arterial pressure at > or =40 mm Hg; resuscitation phase II of 60 mins (from 75 mins to 135 mins) with hemostasis and aggressive fluid resuscitation to normalize hemodynamics; and observation phase III to 72 hrs. Rats were randomly divided into nine groups (n = 6 each) with three rectal temperature levels (38 degrees C [normothermia] vs. 34 degrees C [mild hypothermia] vs. 30 degrees C [moderate hypothermia]) by surface cooling; each with 3 FIO2 levels (0.25 vs. 0.5 vs. 1.0). MEASUREMENTS AND MAIN RESULTS: Hypothermia increased blood pressure compared with normothermia. Increased FIO2 had no effect on blood pressure. Additional blood loss from the tail cut was small, with no differences among groups. Hypothermia and FIO2 of 0.5 decreased visceral hypoxia, as measured by the difference between visceral (liver and jejunum) surface Pco2 and PaCO2 during UHS. Compared with normothermia, mild hypothermia increased the survival time and rate as well as moderate hypothermia (p < .01 by life table), without a significant difference between mild and moderate hypothermia. Increased FIO2 had no effect on survival time or rate. CONCLUSIONS: After severe UHS and resuscitation in rats, mild hypothermia during UHS, compared with normothermia, increases blood pressure, survival time and 72-hr survival rate as well as moderate hypothermia. Mild hypothermia is clinically more feasible and safer than moderate hypothermia. Increased FIO2 seems to have no significant effect on outcome.     

Effect of resuscitative mild hypothermia and oxygen concentration on the survival time during lethal uncontrolled haemorrhagic shock in mechanically ventilated rats.

OBJECTIVE: To test the hypothesis that resuscitative mild hypothermia (MH) (34 degrees C) or breathing fractional inspired oxygen (FIo2) of 1.0 would prolong survival time during lethal uncontrolled haemorrhagic shock (UHS) in mechanically ventilated rats. METHODS: Forty Wistar rats were anaesthetized with halothane, nitrous oxide and oxygen (70/30%), intubated and mechanically ventilated. UHS was induced by volume-controlled blood withdrawal of 3 ml/100 g over 15 min, followed by 75% tail amputation of its length. The animals were randomly divided into four UHS treatment groups (10 rats in each group): group 1 was maintained on an FIo2 of 0.21 and rectal temperature of 37.5 degrees C. Group 2 was maintained on an FIo2 of 0.21 and induced MH. Group 3 was maintained on an FIo2 of 1.0 and 37.5 degrees C. Group 4 was maintained on an FIo2 of 1.0 and MH. Rats were observed otherwise untreated until death. RESULTS: During the initial blood withdrawal, mean arterial pressure (MAP) decreased to 40 mmHg, and the heart rate (HR) increased up to 400 beats/min. The induction of MH increased MAP to 60 mmHg and increased survival time. Moreover, it reduced the HR to 300 beats/min but did not increase bleeding. Ventilation with an FIo2 of 1.0 did not influence MAP, blood loss or survival time, but increased arterial oxygen tension. The mean survival time was 62, 202, 68 and 209 min in groups 1, 2, 3 and 4, respectively. Blood loss from the tail was 1.0, 1.2, 0.9 and 0.7 ml, respectively, in groups 1, 2, 3 and 4. CONCLUSION: MH prolonged the survival time during UHS in mechanically ventilated rats. However, an FIo2 of 1.0 did not influence the survival time or blood loss from the tail.     

低温复苏对大鼠失血性休克肝损伤的影响

目的探讨低温复苏对大鼠失血性休克肝损伤的保护作用及其机制。方法 24只成年雄性Wistar大鼠随机平均分为3组,对照组(S)、常温复苏组(N)(37~38℃)和低温复苏组(H)(33~34℃)。S组只进行外科插管操作,不建立失血性休克模型及复苏,N组和H组在建立失血性休克模型后分别在预定温度下进行复苏。Real-time PCR法检测复苏240 min肝组织PPAR-γ、HSP70和TNF-αm RNA表达变化。ELISA法检测血清TNF-α浓度变化。生化法检测血清ALT和AST浓度变化。结果 (1)休克复苏240 min大鼠血清TNF-α浓度为S组(8.53±1.90)ng/ml,N组(74.08±8.81)ng/ml,H组(32.13±5.82)ng/ml,两个实验组差异具有统计学意义(P<0.05);(2)休克复苏240 min大鼠血清ALT和AST浓度分别为是S组(61±11)U/L、(47±9)U/L,N组(187±20)U/L、(139±15)U/L,H组(141±11)U/L、(97±11)U/L,两个实验组差异有统计学意义(P<0.05);(3)与S组比较,休克复苏240 min N组肝组织PPAR-γm RNA表达量为0.50±0.11,H组PPAR-γm RNA表达量为2.01±0.48(P<0.05);(4)与S组比较,休克复苏240 min N组肝组织HSP70 m RNA表达量为4.12±1.36,H组HSP70 m RNA表达量为11.69±3.88(P<0.05);(5)与S组比较,休克复苏后240 min N组肝组织TNF-αm RNA表达量为15.10±4.99,H组TNF-αm RNA表达量为10.10±2.95(P<0.05)。结论失血性休克后的低温复苏能够上调大鼠肝组织内PPAR-γ和HSP70基因的表达,同时抑制TNF-α基因表达,降低血清中TNF-α、ALT和AST的浓度,减轻肝脏损伤,利于休克的复苏。     

Mild hypothermia during hemorrhagic shock in rats improves survival without significant effects on inflammatory responses

OBJECTIVE: To explore the hypothesis that the survival benefit of mild, therapeutic hypothermia during hemorrhagic shock is associated with inhibition of lipid peroxidation and the acute inflammatory response. DESIGN: Prospective and randomized. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 +/- 0.5 degrees C) or mild hypothermia (33-34 degrees C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: All seven rats in the hypothermia group and seven of 15 rats in the normothermia group survived to 24 hrs (p <.05). Hypothermic rats had lower serum potassium and higher blood glucose concentrations at 90 mins of hemorrhagic shock (p <.05). At resuscitation time 24 hrs, the hypothermia group had less liver injury (based on serum concentrations of ornithine carbamolytransferase and liver histology) and higher blood glucose than the normothermia group (p <.05). There were no differences in serum free 8-isoprostane (a marker of lipid peroxidation by free radicals) between the two groups at either baseline or resuscitation time 1 hr. Serum concentrations of interleukin- 1 beta, interleukin-6, and tumor necrosis factor-alpha peaked at resuscitation time 1 hr. Tumor necrosis factor-alpha concentrations were higher (p <.05) at resuscitation time 1 hr in the hypothermia group compared with the normothermic group. Serum cytokine concentrations were not different between survivors and nonsurvivors in the normothermia group. Serum cytokine concentrations returned to baseline values in both groups by 24 hrs. There were no differences in the number of neutrophils in the lungs or the small intestine between the groups. More neutrophils were found in the lungs at resuscitation time 3 hrs than at resuscitation time 24 hrs in both groups (p <.01). CONCLUSIONS: These data suggest that lipid peroxidation and systemic inflammatory responses to hemorrhagic shock are minimally influenced by mild hypothermia, although liver injury is mitigated and survival improved. Other mechanisms of benefit from mild hypothermia need to be explored.     

Mild or moderate hypothermia but not increased oxygen breathing prolongs survival during lethal uncontrolled hemorrhagic shock in rats, with monitoring of visceral dysoxia.

OBJECTIVE: To test the hypotheses that during lethal uncontrolled hemorrhagic shock (UHS) in rats compared with normothermia and room air breathing: a) mild hypothermia would prolong survival time as well as moderate hypothermia; b) oxygen breathing would prolong survival further; and c) hypothermia and oxygen would mitigate visceral ischemia (dysoxia) during UHS. DESIGN: Prospective, randomized, controlled laboratory animal study. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTION: Fifty-four rats were lightly anesthetized with halothane during spontaneous breathing. UHS was induced by blood withdrawal of 3 mL/100 g over 15 mins, followed by 75% tail amputation with topical application of heparin. Five minutes after tail cut, rats were randomly divided into nine groups (6 rats each) with three rectal temperature levels (38 degrees C [100.4 degrees F; normothermia] vs. 34 degrees C [93.2 degrees F; mild hypothermia] vs. 30 degrees C [86 degrees F; moderate hypothermia]) by surface cooling; each with 3 FIO2 levels (0.25 vs. 0.5 vs. 1.0). Rats were observed without fluid resuscitation until death (apnea and pulselessness). Visceral ischemia was monitored by observing liver and gut surface PCO2. MEASUREMENTS AND MAIN RESULTS: Mean survival time, which was 51 mins in the control group with normothermia and FIO2 of 0.25, was more than doubled with hypothermia, to 119 mins in the combined mild hypothermia groups (p < .05) and to 132 mins in the combined moderate hypothermia groups (p < .05; NS for moderate vs. mild hypothermia). FIO2 had no statistically significant effect on survival time. Increases in visceral surface PCO2 correlated with hypotension (r2 = .22 for intestine and .40 for liver). Transiently, increased FIO2, not hypothermia, mitigated visceral ischemia. CONCLUSIONS: Both mild and moderate hypothermia prolonged survival time during untreated, lethal UHS in rats. Increased FIO2 had no effect on survival. The effects of hypothermia and increased FIO2 during UHS on viscera, the ability to be resuscitated, and outcome should be explored further.     

高渗氯化钠羟乙基淀粉溶液对未控制出血性休克大鼠炎性反应的影响

目的:探讨高渗氯化钠羟乙基淀粉溶液(HHS)对未控制出血性休克(UHS)大鼠炎性反应的影响。方法:采用修订的Capone等方法制备创伤UHS模型。30只SD大鼠随机分为3组:NC组(正常对照组)、NS组(生理盐水复苏组)、HHS组(高渗氯化钠羟乙基淀粉溶液复苏组)。分别在伤后0、30、90、210min观察3组大鼠的心率;血清K+、Na+、Cl-的浓度;血浆TNF-α、IL-1β、IL-6、IL-10的浓度。结果:大鼠休克后心率显著下降,复苏后明显升高;HHS组在伤后90min时,血清Na+、Cl-浓度明显增加(P<0.05),但在伤后210min时恢复正常;两复苏组中TNF-α在休克后迅速升高,复苏后进一步上升,IL-1β与IL-6浓度在伤后90min才有明显增加,而IL-10浓度在伤后210min降低(P<0.05)。与NS组比较,HHS组在各相应时点的TNF-α、IL-1β、IL-6浓度明显下降,IL-10浓度显著增高(P<0.05)。结论:HHS有利于保持UHS大鼠血流动力学稳定,并减少促炎因子释放,促进抗炎因子合成,从而对机体产生一定的保护作用。     

中度低温对急性出血坏死性胰腺炎大鼠胰腺损伤的保护作用

目的 观察中度低温对急性出血坏死性胰腺炎(AHNP)大鼠胰腺损伤和死亡率的影响。方法将112只大鼠随机分为假手术组(n=24)、AHNP常温组(n=44)和AHNP低温组(n=44)。以牛磺胆酸钠逆行注射制备大鼠AHNP模型,低温组诱导AHNP后通过体表降温将体温控制在32.0-33.0℃。各组中24只大鼠分别在AHNP诱导后第2和5 h取标本,观察血清淀粉酶、脂肪酶以及胰腺血管通透性变化、病理形态学改变和胰腺组织湿重／干重比值。AHNP常温组和低温组中余20只大鼠将体温控制在预定范围12 h,观察大鼠72 h的生存率。结果 与AHNP常温组比较,低温组AHNP后2、5 h血清淀粉酶和脂肪酶水平、血管渗透指数及AHNP后5 h胰腺组织水肿程度均明显降低(P均<0.05)。AHNP常温组平均生存时间是7.5 h(3.0-18.0 h),而低温组则延长至25.5 h(13.0-72.0 h)。低温组大鼠生存率显著高于常温组(P=0.000 1)。结论 急性胰腺炎应用中度低温可减轻胰腺损伤,延长大鼠生存时间,提示低温有可能作为一项有益的辅助措施用于急性胰腺炎的治疗中。     

Effect of initial fluid resuscitation on subsequent treatment in uncontrolled hemorrhagic shock in rats

SUMMARY: Using a modified uncontrolled hemorrhage shock model with massive splenic and vascular injury, we evaluated outcome and tissue oxidation injury with different resuscitation interventions during prehospital and hospital phases. The aim of our study was to explore the effect of initial fluid resuscitation on subsequent treatment of uncontrolled hemorrhagic shock in rats. Uncontrolled hemorrhagic shock was produced in 114 Wistar rat by sharp transection both of the splenic parenchyma at one location between the major branches of the splenic artery into the spleen and of one of the major branches of the splenic artery. Experimental design consisted of three phases: a "prehospital phase" (resuscitation with balanced saline to a mean arterial pressure (MAP) of 40, 50, 60, 80, and 100 mmHg, respectively, when MAP reached 30 mmHg), followed by a "hospital phase" (120 min, including control of hemorrhage and resuscitation with balanced saline and whole blood (2:1) or balanced saline alone to a MAP >80 mmHg), and a 240-min observation phase. Blood loss, infused volume, hematocrit, and survival rate were recorded. At the end of the experiment, survivors were sacrificed, and the lung, kidney, and distal ileum were harvested for determination of malondialdehyde (MDA) content and total antioxidative capacity (T-AOC). All rats that were resuscitated to a MAP >80 mmHg in the prehospital phase and received balanced saline alone in the hospital phase died, whereas those that had been resuscitated to a MAP of 40 or 50 mmHg during the prehospital phase and then resuscitated with balanced saline and whole blood in the hospital phase survived throughout the experiment. The animals whose MAP was kept higher than 80 mmHg had significantly higher MDA content and lower T-AOC than those whose MAP was maintained 40, 50, or 60 mmHg during the prehospital phase. In the hospital phase, resuscitation with balanced saline and whole blood not only relieved tissue damage but also improved the survival, as indicated by 44.4% survival rate in the rats that resuscitated to a MAP of 80 or 100 mmHg in the prehospital phase. These results suggested that in our uncontrolled hemorrhagic shock model, limited resuscitation in the prehospital phase had benefit for subsequent treatment in the hospital phase in terms of alleviated tissue damage and improved survivorship.     

Therapeutic hypothermia limited to the resuscitation period does not prolong survival after severe hemorrhagic shock in rats

OBJECTIVE: Controlled hypothermia induced during hemorrhagic shock (HS) has been shown previously to improve survival in HS rat outcome models. We hypothesized that hypothermia (34 degrees C) induced immediately with reperfusion would also improve survival. METHODS: Twenty-four rats were lightly anesthetized with halothane and maintained spontaneous breathing. The rats underwent: an HS phase I of 75 min, with an initial blood withdrawal of 2.5 mL/100 g over 15 min, followed by either additional blood withdrawal or re-infusion in order to maintain a mean arterial pressure (MAP) of 30 mmHg over 60 min; a resuscitation phase II of 60 min with return of shed blood and infusion of lactated Ringer's solution to maintain a MAP of 75 mmHg; and an observation phase III without anesthesia for 72 h. Five minutes before the start of phase II, 12 rats were randomized into either a normothermia (38 degrees C) group or hypothermia (34 degrees C) group. The rectal temperature in each group was carefully maintained during the 60-min period of phase II. Survival at 72 h, as well as gut damage were assessed. RESULTS: All 24 rats survived beyond phases I and II. At 72 h, 8 of 12 rats survived in the hypothermia group, while and 6 of 12 survived in the normothermia group (p=0.64). Intestines of the 72 h survivors were macroscopically normal. In rats that died during phase III, total gut scores did not differ statistically between the groups (1.2+/-0.6 versus 1.0+/-0.9). CONCLUSION: Brief resuscitative hypothermia of 60 min duration induced immediately with reperfusion after HS did not improve survival in this model.     

Increased survival with hypotensive resuscitation in a rabbit model of uncontrolled hemorrhagic shock in pregnancy

Aim

We sought to compare the effects of conservative hypotensive and aggressive normotensive resuscitation strategies on blood loss, fluid requirements, blood lactate and survival rate in a clinically relevant model of uncontrolled hemorrhagic shock in pregnancy.

Method

60 anesthetized New Zealand white rabbits at late gestation underwent uncontrolled hemorrhagic shock by transecting a small artery in the mesometrium, followed by blood withdrawal via the carotid artery, to a mean arterial pressure (MAP) of 40–45 mmHg. They were randomly divided into six groups (n = 10 per group): sham shock (group SS); shock without resuscitation (group SH); hypotensive resuscitation in the simulated prehospital phase with Ringer's solution to MAP of 50, 60, or 70 mmHg, respectively (groups RE50, RE60, RE70); and aggressive resuscitation in the prehospital phase with Ringer's solution to MAP of 80 mmHg (group RE80). Finally, in the simulated hospital phase, animals in the resuscitated groups underwent surgical control of bleeding and were fully resuscitated with half of the heparinized shed blood and Ringer's solution to MAP of 80 mmHg.

Results

Hypotensive resuscitation significantly decreased blood loss and subsequent volume infusion, leading to higher hematocrit, lower lactate concentration, and shorter prothrombin time and activated partial thromboplastin time. Median survival time in group RE60 (4.3 ± 0.6 days) was significantly longer than that in groups RE50 (2.7 ± 0.4 days), RE70 (2.3 ± 0.3 days), and RE80 (1.7 ± 0.3 days) (P < 0.05).

Conclusions

We conclude that in this rabbit model of uncontrolled hemorrhage in pregnancy, hypotensive resuscitation to MAP of 60 mmHg may be an optimal target MAP before hemorrhage can be controlled by surgical intervention.     

不同的复苏压力对非控制失血性休克大鼠肺功能的影响

目的 比较不同的液体复苏压力对非控制失血性休克大鼠肺功能的影响.方法 制备大鼠创伤非控制失血性休克模型.将60只远交群大鼠随机分为6组各10只:NC组为对照组;NF组为休克不复苏组;NS40、NS60(限制性液体复苏组)、NS80、NS100(大量液体复苏组).各液体复苏组在大鼠的平均动脉压(MAP)降至35～40 mm Hg(1 mm Hg=0.133 kPa)时分别给予生理盐水输注,使血压维持在各相应水平.输液1 h后,各液体复苏组均给予手术止血、回输血液及给予足量的液体输注,保持大鼠的MAP≥90 mm Hg.结果 在出血未控制的情况下,限制性液体复苏组的出血量明显低于大量液体复苏组,肺组织病理学损害、酸中毒程度较大量液体复苏组明显减轻.NS60组有9只大鼠存活超过72 h,NS40组3只存活超过72 h,而NF组与NS80、NS100组无一只存活超过72 h.结论 创伤非控制失血性休克及不同的液体复苏压力均可造成不同程度的肺损伤,限制性液体复苏对肺功能具有保护作用.     

不同的复苏压力对非控制失血性休克大鼠肺功能的影响

目的比较不同的液体复苏压力对非控制失血性休克大鼠肺功能的影响。方法制备大鼠创伤非控制失血性休克模型。将60只远交群大鼠随机分为6组各10只：NC组为对照组;NF组为休克不复苏组;NS40、NS60（限制性液体复苏组）、NS80、NS100（大量液体复苏组）。各液体复苏组在大鼠的平均动脉压（MAP）降至35-40mmHg（1mm Hg=0．133kPa）时分别给予生理盐水输注,使血压维持在各相应水平。输液1h后,各液体复苏组均给予手术止血、回输血液及给予足量的液体输注,保持大鼠的MAP≥90mmHg。结果在出血未控制的情况下,限制性液体复苏组的出血量明显低于大量液体复苏组,肺组织病理学损害、酸中毒程度较大量液体复苏组明显减轻。NS60组有9只大鼠存活超过72h,NS40组3只存活超过72h,而NF组与NS80、NS100组无一只存活超过72h。结论创伤非控制失血性休克及不同的液体复苏压力均可造成不同程度的肺损伤,限制性液体复苏对肺功能具有保护作用。     

非控制性失血性休克低压复苏机制新探究

目的 应用大鼠的非控制性失血性休克模型探讨低压复苏在非控制性失血性休克中的机制及意义.方法 大鼠120只,在大鼠失血性休克模型复制成功后随机分为四组:假手术组;休克未处理组;常压复苏组(复苏期控制平均动脉压(MAP)在80 mm Hg以上);低压复苏组[复苏期控制MAP在(60±5)mm Hg].动态观察休克后0.5、1、3、5、7 h大鼠肝组织HSP70、肝脏病理、肝功能、TNF-α、IL-6的变化.HSP70采用Western blot检测其蛋白表达;用RT-PCR观察HSP70 mRNA水平变化的规律.结果 低压复苏组HSP70、TNF-α、IL-6、ALT、TB在休克后升高,较其他组3、5 h时差异有统计学意义(P<0.05),光镜下肝脏淤血、淋巴细胞及中性粒细胞浸润、肝细胞坏死程度都较常压复苏组轻.结论 低压复苏能增强HSP70在非控制性失血性休克后肝组织中的表达,减轻肝脏的继发性损害,同时也表明低压复苏对非控制性失血性休克后肝脏的保护作用与HSP70密切相关.     

Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats

BACKGROUND: In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival. METHODS: An UHS outcome model in rats was used. UHS phase I (90 min) included blood withdrawal of 30 ml/kg over 15 min, followed by tail amputation for uncontrolled bleeding. At 20 min, rats were randomized to four groups (n=10 each) for hypotensive resuscitation from 20 to 90 min (mean arterial pressure [MAP] > or = 40 mmHg): HTS/starch group received 7.2% NaCl/10% hydroxyethyl starch; HTS/albumin group received 7.5% NaCl/20% albumin; HTS/PNA group received 7.5% NaCl/20% PNA; HTS/albumin+tempol group received 7.5% NaCl/20% albumin plus tempol. Resuscitation phase II (180 min) included hemostasis, return of shed blood and administration of fluids to restore MAP > or = 80 mmHg. Observation phase III was to 72 h. RESULTS: The total amount of fluid required to maintain hypotensive MAP during HS was low and did not differ between groups (range: 3.4+/-1.9 to 5.3+/-2.5 ml/kg). The rate of fluid administration required was higher in the HTS/albumin+tempol group compared to all other groups (p=0.006). Additional uncontrolled blood loss was highest in the HTS/PNA group (16.2+/-5.7 ml/kg [p=0.01] versus 10.4+/-7.9 ml/kg in the HTS/starch group, 7.7+/-5.2 ml/kg in the HTS/albumin group and 8.2+/-7.1 ml/kg in the HTS/albumin+tempol group). MAP after start of resuscitation in phase I was lower in the HTS/albumin+tempol group than the HTS/albumin or HTS/PNA groups (p<0.01). This group was also less tachycardic. Long-term survival was low in all groups (2 of 10 after HTS/starch and 1 of 10 after HTS/albumin, 3 of 10 after HTS/PNA, 1 of 10 after HTS/albumin+tempol). Median survival time was shortest in the HTS/albumin+tempol group (72 min [CI 34-190]) compared to all other groups (p=0.01). CONCLUSIONS: Despite its benefits in other model systems, free tempol is potentially hazardous when combined with hypertonic fluids. PNA abrogates these deleterious effects on acute mortality but may lead to increased blood loss in the setting of UHS.     

低体温对创伤失血性休克病人的影响

[目的]通过病例回顾性分析,研究低体温对创伤失血性休克病人的影响及护理。[方法]选择2003年5月—2013年1月我院救治的创伤失血性休克诊断病人100例,根据创伤后体温记录是否出现低温分为低温组33例和无低温组67例。分析两组创伤严重度评分(ISS)、乳酸、pH、凝血酶原时间、失血量、补液量及24h尿量、体温、血压监测及保暖措施等状况。[结果]两组ISS评分、院内出血量、6h输血量、24h补液量、24h尿量和死亡率比较差异有统计学意义(P0.05);对创伤病人体温监测频次明显低于血压的监测频次;保暖措施中95%病历记录采用了棉被保暖,其中15%合并采用了保温毯保温。[结论]临床护理工作中对创伤失血性休克病人的体温观察缺乏规范,易出现护士对创伤失血性休克病人低体温认识不足、监测力度不够、未能及时发现处理的情况,而且保暖方式单一,保温效果不理想。加强对护理工作流程的规范对于创伤失血性休克病人低温的预防、护理具有重要意义。     

未控制出血性休克早期液体复苏的实验研究

目的探讨未控制出血性休克限制性液体复苏的效果.方法Wistar大鼠60只,采用Krausz标准脾脏损伤+切断脾中部一动脉分支制作重度未控制出血性休克模型后,随机分为6组(n=10)未输液复苏组(NF组)及平均动脉压维持在6.67 kPa(1 kPa=7.5 mmHg)组(NS50组)、8.00 kPa组(NS60组)、10.70 kPa组(NS80组)、13.30 kPa组(NS100组)和结扎止血后使平均动脉压维持在13.30 kPa组(止血输液组).各输液组在平均动脉压降至5.33 kPa时开始用平衡盐液复苏,使血压分别维持在各相应水平,观察各组动物的出血量、输液量、存活率、存活时间及各时间点的血压、血乳酸、碱缺失和血细胞比容(Hct)的变化情况.结果NS50组的出血量、输液量明显低于NS80、NS100组(P均<0.05),存活率明显高于NS80、NS100组和未输液组(P均<0.05),存活时间比未输液组、NS80和NS100组明显延长(P均<0.05);随着维持血压的增高,Hct逐渐降低,伤后120分钟NS50组明显高于NS60组、NS80组和NS100组(P均<0.05);在各时间点,血乳酸和碱缺失随着复苏血压的增高而逐渐降低,伤后60分钟,NS50组明显高于NS60组、NS80组、NS100组和止血输液组(P均<0.05).结扎止血组各项指标优于其它各组,与NS50组无显著性差异.结论在重度未控制出血条件下,应限制性液体复苏,止血前仅输入少量液体以维持生命的基本需要,止血后再进行充分的液体复苏,可明显提高存活率,降低出血量.     

创伤非控制失血性休克大鼠限制性液体复苏的实验研究

目的 探讨创伤非控制失血性休克早期限制性液体复苏的效果及适宜的血压范围.方法 采用修订的Capone等方法 制备创伤非控制失血性体克模型.60只SD(Sprague-Dawley,SD)大鼠随机分为6组:NC组,正常对照组;NF组,休克不复苏组;NS40、NS60(限制性液体复苏组)、NS80、NS100组(大量液体复苏组).备液体复苏组在大鼠的平均动脉压(MAP)降至35～40mmHg时分刺给予生理盐水输注,使血压维持在各相应水平.输液1h后,备液体复苏组均给予手术止血、回输血液及给予足量的液体输注,保持大鼠的MAP≥90mmHg.监测出血量、输液量、存活时间、存活率、碱缺失、红细胞比客、心、脑、肾功能指标的变化.结果 创伤失血性休克早期在出血未控的制的情况下,大量液体复苏组(NS80、NS100组)、出血量和输液量明显大于限制性液体复苏组(NS40、NS60组)(P<0.05).NS60组有9/10只大鼠存活超过72h,NS40组3/10只存活起过72h,而NF组与NS80、NS100组无1只存活超过72h.NS40、NS60组大鼠的心、脑、肾病理学损害明显轻于大量液体复苏组.NS40组心、脑、肾病理学改变较NS60组明昱.结论 在有活动性出血的创伤失血性休克早期应给予限制性液体复苏,大鼠早期限制性液体复苏较为适宜的血压范围是MAP保持在55-65mmHg左右(平均60mmHg).