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。     

创伤失血性休克控制性低温的研究进展

创伤后低体温显著增加患者的死亡率,但控制性低温可能改善患者的预后.临床前期研究显示,控制性低温在能量代谢、炎症免疫反应、缺血-再灌注损伤、脏器保护和降低死亡率方面有保护作用,其机制可能与低温降低细胞能量消耗有关.控制性低温有不同的控温方法,并有一定的副作用,在应用时需要加以选择和重视.本文回顾了低温的相关知识及介绍近年来控制性低温对失血性休克的研究进展.     

Induced hypothermia after high-energy soft-tissue injury and subsequent hemorrhagic shock

Many cases of hypothermia (HT) occur in trauma victims subjected to soft tissue injury and hemorrhage. The aim of the present study was to study the effects of HT on the combination of these insults. A standardized gunshot wound was inflicted on the right hind leg of 14 anesthetized piglets. They were then exsanguinated of 50% of their blood volume and randomized to normothermia or HT (30 degrees C). The animals were observed for 4 h after the injury with measurements of hemodynamics, oxygen consumption, and of plasma catecholamines and electrolytes. The insults reduced cardiac output and the arterial pressure by approximately 50%, but no further reduction occurred when HT was induced. The oxygen extraction ratio increased from approximately 35% to 75% in both groups. The gradual reduction of oxygen consumption in HT animals (P < 0.05) decreased the oxygen extraction ratio to around 50%. Heart rate, the serum potassium and creatinine concentrations, and the leukocyte counts were all maintained closer to baseline in the presence of HT. Hypothermia tended to decrease oxygen extraction and was associated with less evidence of tissue injury. These effects are potentially beneficial in soft-tissue trauma combined with hypovolemia.     

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 After shed blood volume (SBV) of 3.25 ml/100 g, withdrawn over 20 min, hemodynamic and respiratory responses were recorded to 3 h and survival to 24 h. The 5 groups of 20 rats each (total n = 100) were as follows: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.     

Treatment with beta-hydroxybutyrate and melatonin is associated with improved survival in a porcine model of hemorrhagic shock

Introduction

The neuroprotective ketone β-hydroxybutyrate (BHB) and the antioxidant melatonin have been found at elevated levels in hibernating mammals. Previous studies in rat models of hemorrhagic shock have suggested a benefit. We compared infusion of 4 M BHB and 43 mM melatonin (BHB/M) to 4 M sodium chloride and 20% DMSO (control solution) to evaluate for potential benefits in porcine hemorrhagic shock.

Methods

Hemorrhagic shock was induced to obtain systolic blood pressures <50 mmHg for 60 min. Pigs were treated with a bolus of either BHB/M (n = 9) or control solution (n = 8) followed by 4-h infusion of the either BHB/M or control solution. All animals were then resuscitated for 20 h after shock. Physiological data were continually recorded, and blood samples were taken at intervals throughout the experiment. Serum samples were analyzed via high resolution NMR for metabolomic response.

Results

BHB/M treatment significantly increased 24-h survival time when compared to treatment with control solution (100% versus 62%; p = 0.050), with a trend toward decreased volume of resuscitative fluid administered to animals receiving BHB/M. BHB/M-treated animals had lower base deficit and higher oxygen consumption when compared to animals receiving control solution. Serum metabolite profiles revealed increases in β-hydroxybutyrate (BHB), succinate, 2-oxovalerate and adipate with BHB/M treatment as compared with animals treated with control infusion.

Conclusion

Infusion of BHB/M conferred a survival benefit over infusion of control solution in hemorrhagic shock. BHB and its products of metabolism are identified in serum of animals subjected to shock and treated with BHB/M. Further preclinical studies are needed to clarify the mechanisms of action of this promising treatment strategy.     

Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model

Introduction

Metabolic dysfunction is one of the hallmarks of sepsis yet little is known about local changes in key organs such as the heart. The aim of this study was to compare myocardial metabolic changes by direct measurements of substrates, such as glucose, lactate and pyruvate, using microdialysis (MD) in in-vivo porcine endotoxemic and hemorrhagic shock. To assess whether these changes were specific to the heart, we simultaneously investigated substrate levels in skeletal muscle.

Methods

Twenty-six female pigs were randomized to three groups: control (C) n = 8, endotoxemic shock (E) n = 9 and hemorrhagic shock (H) n = 9. Interstitial myocardial pyruvate, lactate and glucose were measured using MD. Skeletal muscle MD was also performed in all three groups.

Results

Marked decreases in myocardial glucose were observed in the E group but not in the H group compared to controls (mean difference (CI) in mmol/L: C versus E -1.5(-2.2 to -0.8), P <0.001; H versus E -1.1(-1.8 to -0.4), P = 0.004; C versus H -0.4(-1.1 to 0.3), P = 0.282). Up to four-fold increases in myocardial pyruvate and three-fold increases in lactate were seen in both shock groups with no differences between the two types of shock. There was no evidence of myocardial anaerobic metabolism, with normal lactate:pyruvate (L:P) ratios seen in all animals regardless of the type of shock.In skeletal muscle, decreases in glucose concentrations were observed in the E group only (mean difference: C versus E -0.8(-1.4 to -0.3), P = 0.007). Although skeletal muscle lactate increased in both shock groups, this was accompanied by increases in pyruvate in the E group only (mean difference: C versus E 121(46 to 195), P = 0.003; H versus E 77(7 to 147), P = 0.032; C versus H 43(-30 to 43), P = 0.229). The L:P ratio was increased in skeletal muscle in response to hemorrhagic, but not endotoxemic, shock.

Conclusions

Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels. Despite the decrease in glucose, myocardial lactate and pyruvate concentrations were elevated and not different than in hemorrhagic shock. In skeletal muscle, substrate patterns during endotoxemic shock mimicked those seen in myocardium. During hemorrhagic shock the skeletal muscle response was characterized by a lack of increase in pyruvate and higher L:P ratios.Hence, metabolic patterns in the myocardium during endotoxemic shock are different than those seen during hemorrhagic shock. Skeletal muscle and myocardium displayed similar substrate patterns during endotoxemic shock but differed during hemorrhagic shock.     

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 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.     

Potential role of therapeutic hypothermia in the salvage of traumatic hemorrhagic shock

Although therapeutic hypothermia could serve as a potential therapeutic strategy for treatment of traumatic hemorrhagic shock, significant controversy exists regarding its safety and feasibility. The current resuscitation strategy in traumatic hemorrhagic shock may also require updating. In this article, we have carried out an extensive literature search in this field and propose an initial algorithm for use of therapeutic hypothermia in traumatic hemorrhagic shock. This work lays essential groundwork for future investigations in this field.     

多发创伤合并休克导致大鼠多器官功能障碍综合征的实验研究

目的：探讨造成大鼠一次打击型多器官功能障碍综合征（ＭＯＤＳ）所需的创伤条件。方法：５６只ＳＤ大鼠随机分为５组：假手术组（Ｎ）、低血容量性休克组（Ｓ）、２处创伤合并休克组（Ｂ）、４处创伤合并休克组（Ｃ）和６处创伤合并休克组（Ｄ）,用各脏器生化检测指标及脏器受损数来评价各组动物各脏器的功能。结果：Ｎ、Ｓ组复苏后７２小时内无一只动物死亡,不发生多器官损伤（ＭＯＩ）和衰竭（ＭＯＦ）;Ｂ、Ｃ组７２小时内极少死亡（仅Ｃ组死亡１只）,ＭＯＩ发生率分别为３７．５％和８７．５％,ＭＯＦ发生率分别为０和１２．５％;Ｄ组均于７２小时内死亡,复苏成功的动物平均存活（３２．３±９．３）小时,且全部发生ＭＯＩ,ＭＯＦ的发生率达９５．０％。结论：６处创伤合并休克可导致一次打击型ＭＯＤＳ。     

Increased poly(ADP-ribose) polymerase activity during porcine hemorrhagic shock is transient and predictive of mortality

AIM OF THE STUDY: The aim of our study was to compare poly(ADP-ribose) polymerase (PARP) activity levels in a porcine model of hemorrhagic shock and resuscitation. MATERIALS AND METHODS: We designed a prospective, comparative randomized survival study of hemorrhagic shock using 20 male Yorkshire-Landrace pigs (15-25 kg). In 16 pigs after splenectomy, we induced hemorrhagic shock to a mean arterial pressure of 50 mm Hg ( approximately 35% bleed). Pigs were randomized to receive normotensive resuscitation (SBP 90 mm Hg), mild hypotensive resuscitation (SBP 80 mm Hg), moderate hypotensive resuscitation (SBP 65 mm Hg), or no resuscitation (n=4 in each group). We also included a group of sham animals that were instrumented and had a splenectomy but not bled (n=4). Muscle and liver biopsies were taken prior to hemorrhage, after 45 min of shock, and 8, 24, and 48 h after resuscitation. PARP activity levels in biopsies were measured using chemical quantitation of NAD+. RESULTS: Irrespective of our resuscitation strategy or outcome, both muscle and liver PARP activity levels rose after 45 min of shock and then returned to baseline. Excluding our control animals, PARP activity levels were significantly higher during shock in non-survivors compared to survivors. CONCLUSIONS: In our model of porcine hemorrhagic shock, PARP activity levels increased during hemorrhagic shock. However, this increase in PARP activity levels was transient as they returned to baseline regardless of resuscitation strategy. Interestingly, PARP activity levels were significantly higher during hemorrhagic shock in non-survivors compared to survivors. These findings suggest that PARP activity may be a part of initial pathways leading from hemorrhagic shock to death.     

Plasma levels of liver-specific miR-122 is massively increased in a porcine cardiogenic shock model and attenuated by hypothermia

Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n = 6) or normothermia (38°C, n = 6). Circulating miRNAs were extracted from plasma and measured with quantitative real-time polymerase chain reaction (PCR). Tissue specificity was assessed by miRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific, whereas miR-208b was expressed exclusively in the heart. In the control group, ischemic cardiogenic shock induced a 460,000-fold and a 63,000-fold increase in plasma levels of miR-122 (P < 0.05) and miR-208b (P < 0.05), respectively. Therapeutic hypothermia significantly diminished the increase in miR-122 compared with the normothermic group (P < 0.005). In our model, hypothermia was initiated after coronary reperfusion and did not affect either myocardial damage as previously assessed by magnetic resonance imaging or the plasma level of miR-208b. Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.     

Effects of mild hypothermia on survival and serum cytokines in uncontrolled hemorrhagic shock in rats

Previous studies have suggested benefit of mild hypothermia during hemorrhagic shock (HS). This finding needs additional confirmation and investigation into possible mechanisms. Proinflammatory cytokines are mediators of multiple organ failure following traumatic hemorrhagic shock and resuscitation. We hypothesized that mild hypothermia would improve survival from HS and may affect the pro- and anti-inflammatory cytokine response in a rat model of uncontrolled HS. Under light halothane anesthesia, uncontrolled HS was induced by blood withdrawal of 3 mL/100 g over 15 min followed by tail amputation. Hypotensive (limited) fluid resuscitation (to prevent mean arterial pressure [MAP] from decreasing below 40 mmHg) with blood was started at 30 min and continued to 90 min. After hemostasis and resuscitation with initially shed blood and Ringer's solution, the rats were observed for 72 h. The animals were randomized into two HS groups (n = 10 each): normothermia (38 degrees C +/- 0.5 degrees C) and mild hypothermia (34 degrees C +/- 0.5 degrees C) from HS 30 min until resuscitation time (RT) 60 min; and a sham group (n = 3). Venous blood samples were taken at baseline, RT 60 min, and days 1, 2, and 3. Serum interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha concentrations were quantified by ELISA. Values are expressed as median and interquartile range. Survival time by life table analysis was greater in the hypothermia group (P = 0.04). Survival rates to 72 h were 1 of 10 vs. 6 of 10 in the normothermia vs. hypothermia groups, respectively (P = 0.057). All cytokine concentrations were significantly increased from baseline at RT 60 min in both HS groups, but not in the shams. At RT 60 min, in the normothermia vs. hypothermia groups, respectively, IL-1beta levels were 185 (119-252) vs. 96 (57-135) pg/mL (P = 0.15); IL-6 levels were 2242 (1903-3777) vs. 1746 (585-2480) pg/mL (P = 0.20); TNF-alpha levels were 97 (81-156) vs. 394 (280-406) pg/mL (P= 0.02); and IL-10 levels were 1.7 (0-13.3) vs. 15.8 (1.9-23.0) pg/mL (P = 0.09). IL-10 remained increased until day 3 in the hypothermia group. High IL-1beta levels (>100 pg/mL) at RT 60 min were associated with death before 72 h (odds ratio 66, C.I. 3.5-1255). We conclude that mild hypothermia improves survival time after uncontrolled HS. Uncontrolled HS induces a robust proinflammatory cytokine response. The unexpected increase in TNF-alpha with hypothermia deserves further investigation.     

环境低温对非麻醉猪失血性休克血流动力学及氧代谢的影响

目的 探讨环境低温对非麻醉猪失血性休克血流动力学及氧代谢的影响.方法 沈阳军区总医院动物中心提供的巴马香猪16头随机(随机数字法)分为:室温休克组和低温休克组,每组8头.按30 mL/kg放血建立失血性休克模型,记录建模前及建模后4h内不同时点的核心体温、心率、平均动脉压、中心静脉压、心输出量、混合静脉血氧饱和度及血气等变化,并计算氧摄取率、氧供指数和氧耗指数.采用SPSS11.0软件包行计量资料的成组t检验.结果 模型建立后室温组动物的核心体温略有下降,环境低温使核心体温下降更加明显.低温组动物的病死率较室温组明显增加(P＜0.05).休克导致氧供和氧耗明显下降.室温组和低温组的血流动力学指标、氧供和氧耗的差异无统计学意义,但两者在pH值、乳酸和氧提取率上差异具有统计学意义(P＜0.05).结论 环境低温加重了失血性休克后的氧代谢紊乱,使预后进一步恶化.     

控制性低温对兔创伤失血性休克早期肺炎症反应的影响

目的探讨控制性低温对兔创伤失血性休克后早期肺部炎症反应和对肺组织损伤程度的影响。方法24只健康新西兰大白兔,随机分为正常对照组(C组)、常温组(N组)、浅低温组(MIH组)、中低温组(MOH组),每组6只。采用ELISA法测定肺组织匀浆上清液TNF-α、IL-6、IL-8、IL-10含量及肺水含量。结果创伤失血性休克后8h,肺组织匀浆TNF-α、IL-6、IL-8、IL-10含量均显著升高;MIH组和MOH组TNF-α含量低于N组(P<0.05),但组间差异无统计学意义;MIH组和MOH组肺组织IL-6含量显著低于N组(P<0.01);MIH组肺组织IL-8含量显著低于N组和MOH组(P<0.01),MOH组肺组织IL-8含量低于N组,但差异无统计学意义;MIH组和MOH组肺组织IL-10含量均显著低于N组。创伤失血性休克后早期总肺水含量显著升高,MIH组和MOH组总肺水含量低于N组(P<0.01)。结论不同程度的控制性低温对创伤失血性休克后早期肺促炎反应和抗炎反应均有抑制作用,对创伤失血性休克后的肺组织也有一定的保护作用。浅低温对创伤后肺组织炎症反应和抗炎反应的抑制作用强于中低温,而且其可控性强,副作用相对较少,因此,浅低温更有益于创伤失血性休克后早期肺组织的保护。     

低温对失血性休克炎症小体活化的影响研究

目的 探索治疗性低温对失血性休克(hemorrhagic shock,HS)大鼠肺组织炎症小体活化的影响.方法 本研究将24只SD大鼠随机(随机数字法)分成3组:假手术组,常温液体复苏(normothermia resuscitation,NR)组,低温液体复苏(hypothermia resuscitation,HR)组.各组通过股动脉放血到平均动脉压达40 mmHg(1 mmHg=0.133 kPa)保持1h建立HS模型,随后NR组和HR组通过液体复苏使平均动脉压达90 mmHg,维持1h,4h后通过放血处死各组大鼠,留取大鼠肺组织.经苏木精-伊红(HE)染色于光镜下观察肺组织的损伤程度,使用于湿比重法检测肺组织水肿情况,采用RT-PCR和Western blotting检测肺组织炎症小体NLRP-3、Caspase-1、IL-1βmRNA和蛋白表达水平.多组间比较采用方差分析,组间两两比较采用SNK-q检验,以P＜0.05为差异具有统计学意义.结果 (1) HE染色结果示,与NR组相比,HR组急性肺损伤程度明显较低.(2)肺组织湿/干比重与HR组相比NR组肺水肿显著降低,HR组(5.85 ±0.10);NR组(6.47±0.17),t=3.14,P＜0.05;(3)与NR组相比,HR组的NLRP-3和Caspase-1的蛋白表达均显著减少;(4)与NR组相比,HR组的NLRP-3 mRNA表达水平显著降低,HR组(1.027±0.143),NR组(1.349 ±0.163),t=4.36,P＜0.05;HR组的IL-1β mRNA表达水平显著降低,HR组(1.623±0.125),NR组(2.388±0.229),t=7.72,P＜0.05.结论 治疗性低温能够降低炎症小体信号通路的活化,从而减弱HS诱导的肺组织损伤.