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Medicina

由脑氧测量和猪期扩展血液动力学监测指导的标准化出血性休克诱导

Published: May 21, 2019
doi:
10.3791/59332
, , , , , ,
1Department of Anesthesiology,University Medical Center of the Johannes Gutenberg-University

Summary

出血性休克是严重受伤患者的严重并发症,导致氧气供应不足,危及生命。提出了一种标准化的方法,通过猪的采血诱导出血性休克,由血液动力学和微循环脑氧合指导。

Abstract

出血性休克是严重伤害相关死亡的主要原因之一。循环量和氧气载体的丢失可能导致氧气供应不足和不可逆的器官衰竭。大脑只施加有限的补偿能力,特别有严重的缺氧损伤风险。本文通过计算血退血的方法,论证了猪模型中危及生命的出血性休克的可重复诱导。我们通过近红外光谱和扩展血液动力学监测来对冲击感应进行分子,以显示系统性循环衰竭以及脑微循环氧耗竭。与主要侧重于冲击感应的预定义去除体积的类似模型相比,这种方法通过由此产生的宏观和微循环失败来突出滴定。

Introduction

大量失血是导致1、2、3等1、2、3人死亡的主要原因之一。循环液和氧气载体的丢失会导致血液动力学故障和严重供氧不足,并可能导致不可逆的器官衰竭和死亡。休克的严重程度受其他因素影响,如体温过低、凝血病和酸中毒4。特别是大脑,也肾脏缺乏补偿能力,由于高氧需求和缺乏足够的厌氧能量第5、6代。出于治疗目的,快速和即时的行动至关重要。在临床实践中,使用平衡电解质溶液的液体复苏是治疗的首选,其次是红细胞浓缩液和新鲜冷冻血浆的分管。血栓细胞浓缩物、儿茶酚胺、凝固和酸碱状态的优化支持治疗在持续创伤后恢复正常的生理状况。这一概念侧重于恢复血液动力学和宏观循环。然而,一些研究表明,微循环灌注不能与宏观循环同时恢复。特别是,脑灌注仍然受损,进一步缺氧可能发生7,8。

使用动物模型使科学家能够建立新颖或实验性的策略。猪和人类的可比解剖学、同源性和生理学使得对特定病理因素有结论。两个物种都有类似的代谢系统和对药理治疗的反应。与小动物模型相比,这是一个很大的优势,在血量、血液动力学和整体生理学上的差异使得几乎不可能模仿临床场景9。此外,授权的医疗设备和消耗品可以很容易地用于猪模型。此外,它很容易从商业供应商获得猪,这允许遗传和表型的高度多样性,并降低成本10。通过血管排泄的采血模式相当常见,11、12、13、14、15。

在这项研究中,我们通过动脉血液戒断扩展出血性休克诱导的概念,精确滴定血液动力学衰竭和脑氧合损伤。如果心脏指数和平均动脉压力下降到基线值的40%以下,则达到出血性休克,这已被证明会导致脑区域氧合饱和度严重恶化8。脉冲轮廓心脏输出 (PiCCO) 测量用于连续血液动力学监测。首先,系统必须通过肺热稀释进行校准,从而能够计算血管外肺水含量和全球端结节量的心脏指数。随后,通过脉冲轮廓分析计算连续心脏指数,并提供脉冲压力和行程体积变化等动态预载量参数。

该技术在临床和实验环境中已经确立。近红外光谱(NIRS)是一种临床和实验性的建立方法,用于实时监测脑氧供应的变化。自附着式传感器连接到左右额头,在大脑前额皮层中无创地计算脑氧合。两个波长的红外光(700和900nm)在从皮层组织反射后由传感器发射和检测。为了评估脑氧含量,动脉和静脉血的贡献以1:3关系计算,并每隔5秒更新。深度为 1-4 厘米的灵敏度呈指数级递减,受渗透组织(如皮肤和骨骼)的影响,尽管头骨与红外光呈半透明。该技术促进快速治疗行动,以防止患者出现不良结果,如精神错乱或缺氧脑损伤,并作为目标参数的情况下,心脏输出受损16,17。在实验休克期间,这两种技术的结合使宏观循环以及脑微循环损伤的精确滴定,从而研究这种危及生命的事件。

Protocol

这一议定书的实验得到了国家和机构动物照料委员会的批准(德国科布伦茨州兰登苏松桑特莱茵兰-普法尔茨;主席:西尔维亚·艾施-沃尔夫博士;参考号: 23 177-07/G 14-1-084;02.02.2015. 实验根据《活体实验动物研究报告》(ARRIVE)指南进行。该研究计划于2015年11月至2016年3月进行。经过文献研究,猪模型被选作出血性休克的成熟模型。七只麻醉雄猪(Susscrofa驯养)的平均重量为28~2公斤,年龄为2-3个月。这些动…

Representative Results

启动冲击感应后,可以登记较短的补偿时间。随着持续采血,上述心循环减损,监测crSO2,心脏指数,胸腔内血量指数,和全球端舒张体积指数(图2,图 3和图 4。此外,心动过速和动脉血压下降是出血性休克的常见表现(图2)。描边体积变化显著增加 (图 3.血管外肺?…

Discussion

该协议描述了一种通过控制性动脉出血诱导出血性休克的方法,该方法由全身血液动力学和脑微循环损伤指导。冲击条件通过计算25-35 mLkg-1的计算,并通过上述代理参数的复合证实,表明心脏循环失败。如果不加以治疗,这个程序在2小时内在66%的动物中是致命的,这突出了模型的严重性和可重复性。适当的液体复苏,另一方面,重新稳定循环,并批准对仿生临床方案8的重提。然而,…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

作者要感谢达格玛·迪尔文斯基斯的出色技术支持。

Materials

3-way-stopcock blue Becton Dickinson Infusion Therapy AB Helsingborg, Sweden 394602 Drug administration
3-way-stopcock red Becton Dickinson Infusion Therapy AB Helsingborg, Sweden 394605 Drug administration/Shock induction
Atracurium Hikma Pharma GmbH , Martinsried AM03AC04* Anesthesia
Canula 20 G Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain 301300 Vascular access
Datex Ohmeda S5 GE Healthcare Finland Oy, Helsinki, Finland – Hemodynamic monitor
Desinfection  Schülke & Mayr GmbH, Germany 104802 Desinfection 
Heidelberger Verlängerung 75CM Fresenius Kabi Deutschland GmbH 2873112   Drug administration/Shock induction
INVOS 5100C Cerebral Medtronic PLC, USA – Monitore for cerebral regional oxygenation 
INVOS Cerebral/Somatic Oximetry Adult Sensors Medtronic PLC, USA 20884521211152 Monitoring of the cerebral regional oxygenation 
Endotracheal tube Teleflex Medical Sdn. Bhd, Malaysia 112482 Intubation
Endotracheal tube introducer   Wirutec GmbH, Sulzbach, Germany 5033062 Intubation
Engström Carestation GE Heathcare, Madison USA – Ventilator
Fentanyl Janssen-Cilag GmbH, Neuss AA0014* Anesthesia
Gloves Paul Hartmann, Heidenheim, Germany 9422131 Self-protection
Incetomat-line 150 cm Fresenius, Kabi GmbH, Bad Homburg, Germany 9004112 Drug administration
Ketamine Hameln Pharmaceuticals GmbH, Zofingen, Schweiz AN01AX03* Sedation
Laryngoscope Teleflex Medical Sdn. Bhd, Malaysia 671067-000020 Intubation
Logical pressure monitoring system Smith- Medical GmbH,  Minneapolis, USA MX9606 Hemodynamic monitor
Logicath 7 Fr 3-lumen 30cm Smith- Medical GmbH,  Minneapolis, USA MXA233x30x70-E Vascular access/Drug administration
Masimo Radical 7 Masimo Corporation, Irvine, USA – Hemodynamic monitor
Mask for ventilating dogs Henry Schein, Melville, USA 730-246 Ventilation
Original Perfusor syringe 50ml Luer Lock B.Braun Melsungen AG, Melsungen, Germany 8728810F Drug administration
PICCO Thermodilution. F5/20CM EW  MAQUET Cardiovascular GmbH, Rastatt, Germany PV2015L20-A   Hemodynamic monitor
Percutaneous sheath introducer set 8,5 und 9 Fr, 10 cm with integral haemostasis valve/sideport Arrow international inc., Reading, USA AK-07903 Vascular access/Shock induction
Perfusor FM Braun B.Braun Melsungen AG, Melsungen, Germany 8713820 Drug administration
Potassium chloride Fresenius, Kabi GmbH, Bad Homburg, Germany 6178549 Euthanasia
Propofol 2% Fresenius, Kabi GmbH, Bad Homburg, Germany   AN01AX10* Anesthesia
 Pulse Contour Cardiac Output (PiCCO2)  Pulsion Medical Systems, Feldkirchen, Germany – Hemodynamic monitor
Sonosite Micromaxx Ultrasoundsystem Fujifilm, Sonosite Bothell, Bothell, USA  – Vascular access
Stainless Macintosh Size 4 Teleflex Medical Sdn. Bhd, Perak,  Malaysia 670000 Intubation
Sterofundin B.Braun Melsungen AG, Melsungen, Germany AB05BB01* balanced electrolyte infusion
Stresnil 40mg/ml   Lilly Germany GmbH, Wiesbaden, Germany QN05AD90 Sedation
Syringe 10 mL Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain 309110 Drug administration
Syringe 2 mL Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain 300928 Drug administration
Syringe 20 mL Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain 300296 Drug administration
Syringe 5 mL Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain 309050 Drug administration
venous catheter 22G B.Braun Melsungen AG, Melsungen, Germany 4269110S-01 Vascular access
*ATC:  Anatomical Therapeutic Chemical / Defined Daily Dose Classification 
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Tags

Hemorrhagic ShockCerebral OximetryHemodynamic MonitoringFluid ResuscitationCoagulationCatecholamine TherapyNear Infrared SpectroscopySeldinger TechniqueFemoral ArteryFemoral VeinIntroducer SheathCentral Venous LinePulse Contour Cardiac Output

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Ziebart, A., Kamuf, J., Ruemmler, R., Rissel, R., Gosling, M., Garcia-Bardon, A., Hartmann, E. K. Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs. J. Vis. Exp. (147), e59332, doi:10.3791/59332 (2019).
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