儿茶酚胺相关的毛细血管渗漏课件.ppt

1、Hello !儿茶酚胺相关的毛细血管渗漏儿茶酚胺相关的毛细血管渗漏许汪斌昆明医科大学第一附属医院重症医学科? 主要内容： Case Report 内源性儿茶酚胺释放/毛细血管渗漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker ?Abel vanderschuren, et al. J. Neurosurg 110: 64-66. 2009 52岁的女性（Wt 50 kg），既往无任何心血管疾病，左大脑前动脉的动脉瘤破裂，蛛网膜下腔出血（Fisher Grade 4 SAH），GCS 4分。 入院后检查：HR 115 bpm, ST? , avL,

2、 V4-6 1 mm，QTc延长，心肌酶轻度升高（Troponin-?0.19 ng/mL），SBP从 125 mm Hg快速下降到80 mm Hg。 急性肺水肿，肢端发冷，紫绀，给予经口气管插管，呼吸机支持，FiO20.6。 严重的左心功能不全（心脏射血分数18%），Swan-Ganz 导管监测：CO 1.9 L/min, SvO244%。SAH所导致的心功能损伤? 主要内容： Case Report 内源性儿茶酚胺释放/毛细血管渗漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker ? 重型颅脑损伤的病人，抽搐之后极易发生肺水肿（Neurogen

3、ic pulmonary edema）。? SAH相关的心肌损伤（Stress-induced cardiomyopathy）。? 美军越战时期的医疗报告,合并有横断性颈脊髓受伤的颅脑创伤的士兵没有肺水肿的发生。? 动物实验： 动物实验显示高颅压可导致血浆的肾上腺素含量呈200?1000倍的增加。 去除支配心脏的交感神经、或经-阻滞剂预处理后，动物的心脏可免于SAH所导致的损伤。? 临床研究： SAH发病后尽快给予-阻滞剂(Labetalol)治疗，有利于减轻应激性心肌损伤的并发症。 血浆儿茶酚胺水平与颅脑创伤的死亡率有直接的相关性。Woolf PD, et al. The predictiv

4、e value of catecholamines in assessing outcome in traumatic brain injury. J neurosurg 1987; 66: 875-82.SAH在发病后48小时内血浆的去甲肾上腺素含量显著增加并持续1周，血浆去甲肾上腺素含量回落到正常的水平需要6个月。Two-pore model for fluid exchangeby Rippe and Haraldsson, 1994fluid and small solutesproteinfluid proteins and small solutesplasmaDpDPsmall

5、porelarge pore Dp=0interstitiumDPJv = KfPc -Jv = KfPc -PiPiPlasma volume loss at 2 different levels of MAP (difference 12-15 mmHg) at increased permeability after 3 hrs? ? ?(ml/kg)1412108642(n=11)(n=11)(n=11)(n=11)Pc MAPControlAlbumin15 ml/kg NoradrenalinAlbumin 15 ml/kg + NA（Rat with sepsis）By Per-

6、Olof Grande? 重度颅脑损伤的儿茶酚胺风暴（重度颅脑损伤的儿茶酚胺风暴（Catecholamine surge）： 重度重度TBI的神经重症管理不仅应重视继发性脑损伤，还应改善随的神经重症管理不仅应重视继发性脑损伤，还应改善随应激反应而激活的交感神经所导致的毛细血管渗漏。应激反应而激活的交感神经所导致的毛细血管渗漏。大量的内源性儿茶酚胺释放大量的内源性儿茶酚胺释放全身性毛细血管渗漏低血容量灾难性低血压灾难性低血压? 毛细血管渗漏的评估： 昆明医科大学第一附属医院重症医学科的方法：? Alb+ Alb/Glo? (Hct - Alb )Xus index：? （Hct 40?45% A

7、lb 35-50 g/L）Hct - Alb5V RBC V Serum protein毛细血管渗漏，大量的血浆蛋白外漏，血浆白蛋白（Albumin, Alb.）降低，伴随血液的抽缩，血球压积的增高（Haematocrit, Hct.）。（Hct - Alb）? Quantification of Capillary Leakage -By Xus Index-HCT - ALB 5V RBC V Serum proteinHematocrit and plasma albumin levels difference may be a potential biomarker to discri

8、minate preeclampsia and eclampsia in patients with hypertensive disorders of pregnancy . accepted in Clinica Chimica Acta in 1 Dec 2019.? 主要内容： Case Report 内源性儿茶酚胺释放/毛细血管渗漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker BBB损伤所导致的血管性水肿缺氧所导致的细胞毒性水肿Per-Olof Gr?ndePc MAP，血管性水肿脑血管自动调节功能的损伤脑血流量AA1A2脑灌注压By

9、 Nordstrom CH.脑血管自动调节功能的损伤脑血流量AA1A2脑灌注压piglet with TBIBy Nordstrom CH.脑血管自动调节功能的损伤脑血流量CBAA1A2脑灌注压piglet with bacterial meningitisBy Nordstrom CH.Pc 1 mmHgICP 8 mmHgIntracranial pressure (mmHg)baselineElevated blood pressureBaseline blood pressurebaselineEffects of increase in blood pressure (30 mmHg

10、) on ICP（cat with bacterial meningitis）Elevated blood pressureElevated blood pressureBy Per-Olof GrandeBaseline blood pressureLund concept for CPP in TBI脑血流量CBAA1A2?CPP 70 mm HgCPP 50?60 mm Hg脑灌注压BBB损伤所导致的血管性水肿缺氧所导致的细胞毒性水肿Per-Olof Gr?nde? Q = CPP/R 问题的提出：? 谁对损伤区域血流灌注的影响最大？R CPP缩血管药物（VASOCONSTRICTORS

11、 ）have adverse effects not only by compromising circulation of the penumbra zone, but also by increasing the loss of plasma to the interstitiumAvoid Stress and hyperventilationas they both may induce vasoconstrictionof the penumbra zonesevere head injury? 降低机体的应激反应/内源性儿茶酚胺释放: 在颅脑创伤病人还未转入ICU之前，就应主动的给

12、予镇静镇痛的治疗（安定类药物 + 阿片类药物），以有效的降低机体的应激反应。 转入ICU之后，进一步的降低机体的应激反应，以及体内的儿茶酚胺的释放，给予咪唑安定 + 芬太尼 + ?1受体阻断剂美托洛尔 + ?2受体激动剂可乐定。? 降低脑毛细血管的静水压+ 抗应激： ?1受体拮抗剂美托洛尔+ 中枢性的?2激动剂可乐定维持CPP 50?60 mm Hg (metoprolol + clonidine)NORDSTROM, C.H., REINSTRUP, P., XU, W., et al.(2019). Assessment of the lower limit for cerebral pe

13、rfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology 98, 809-814.? 主要内容： Case Report 内源性儿茶酚胺释放/毛细血管渗漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker J Trauma. 2019;62:2635Conclusions: 1. Beta-blocker exposure was associated with a significant r

14、eduction in mortality in patients with severe TBI. 2. This reduction in mortality is even more impressive, considering that the BB(+) group was older, more severely injured, and had lower predicted survival.NICU救治年龄?55岁的重型颅脑创伤，给予1受体阻剂的治疗，死亡率从60%降致28%。Kenji Inaba, et al. Beta-Blockers in isolated blu

15、nt head injury. J Am Coll Surg 2019; 206: 432-38.Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity After Brain Injury? 治疗：治疗： -blockers + ?2- agonists + morphine + baclofen + gabapentin 急性发作期：急性发作期：morphine + short-acting benzodiazepines A balance between control of symptoms without o

16、ver sedation is the goal.Curr Neurol Neurosci Rep.2019V13N8 :370J Neurosci Nurs.2019V48N2 :82-9调查调查30003000例患者（创伤、脓毒症、心梗、心脏骤停后综合征），例患者（创伤、脓毒症、心梗、心脏骤停后综合征），发现具有共同的病理生理改变发现具有共同的病理生理改变内皮损伤内皮损伤sympatho-adrenal hyperactivationEndotheliopathy & capillary leakage (endothelial cell and glycocalyx damage)内皮损

17、伤的程度与儿茶酚胺的浓度成正比！内皮损伤的程度与儿茶酚胺的浓度成正比！毛细血管渗漏和凝血功能紊乱是内皮损伤最终结果！毛细血管渗漏和凝血功能紊乱是内皮损伤最终结果！Endogenous heparinization due to the shedding of the glycocalyx （syndecan-1）内皮损伤的治疗：内皮损伤的治疗：intravenous beta-blockers +1. Xu L, et al. Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation

18、disorders in rats with acute traumatic coagulopathy. Blood Coagul Fibrinolysis. 2019;26:15260. 2. Chatterjee S, et al. Early intravenous beta-blockers in patients with acute coronary syndromea meta-analysis of randomized trials. Int J Cardiol. 2019;168(2):915213. Morelli A, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2019;310(16):168391.Thanks for your attention!Shangri-La的松赞林寺