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1、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, V4-6 1 mm，QTc延长，心肌酶轻度
2、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，FiO2 0.6。 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, SvO2 44%。,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（Neurogenic pulmonary edema）。 S
3、AH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2001000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 predictive value of catecholamines
4、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。,fluid and small solutes,protein,fluid proteins and small solutes,interstitium,plasma,small pore,large pore,DP,Dp,DP,Dp=0,Two-pore model for fluid exchange by Rippe
5、and Haraldsson, 1994,Jv = KfPc - Pi,Control,Noradrenalin,(n=11),(n=11),Plasma volume loss at 2 different levels of MAP (difference 12-15 mmHg) at increased permeability after 3 hrs,(ml/kg),Albumin15 ml/kg,Albumin 15 ml/kg + NA,2,4,6,8,10,12,14, ,(n=11),(n=11),By Per-Olof Grande,（Rat with sepsis）,Pc
6、MAP,重度颅脑损伤的儿茶酚胺风暴（Catecholamine surge）： 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,全身性毛细血管渗漏,低血容量,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 4045% Alb 35-50 g/L）,Hct - Alb5,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（Haematocr
7、it, Hct.）。,（Hct - Alb）,V RBC V Serum protein,Quantification of Capillary Leakage -By Xus Index -HCT - ALB 5,Hematocrit and plasma albumin levels difference may be a potential biomarker to discriminate preeclampsia and eclampsia in patients with hypertensive disorders of pregnancy . accepted in Clini
8、ca Chimica Acta in 1 Dec 2016.,V RBC V Serum protein,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,Per-Olof Grnde,缺氧所导致的细胞毒性水肿,BBB损伤所导致的血管性水肿,Pc MAP，血管性水肿,脑灌注压,脑血流量,A,A1,A2,脑血管自动调节功能的损伤,By Nordstrom CH.,脑灌注压,脑血流量,A,A1,A2,脑血管自动调节功能的损伤,piglet with TBI,By Nordstrom C
9、H.,脑灌注压,脑血流量,A,A1,A2,B,C,脑血管自动调节功能的损伤,piglet with bacterial meningitis,By Nordstrom CH.,Pc 1 mmHg,ICP 8 mmHg,Intracranial pressure (mmHg),baseline,Elevated blood pressure,Baseline blood pressure,baseline,Elevated blood pressure,Elevated blood pressure,Baseline blood pressure,Effects of increase in b
10、lood pressure (30 mmHg) on ICP,By Per-Olof Grande,（cat with bacterial meningitis）,脑灌注压,脑血流量,A,A1,A2,B,C,Lund concept for CPP in TBI, CPP 70 mm Hg,CPP 5060 mm Hg,Per-Olof Grnde,缺氧所导致的细胞毒性水肿,BBB损伤所导致的血管性水肿,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） have adverse effects not only by
11、 compromising circulation of the penumbra zone, but also by increasing the loss of plasma to the interstitium,Avoid Stress and hyperventilation as they both may induce vasoconstriction of the penumbra zone,severe 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
12、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 5060 mm Hg (metoprolol + clonidine) NORDSTROM, C.H., REINSTRUP, P., XU, W., et al.(2003). Assessment of the lower limit for cerebral perfusion pressure in severe head inj
13、uries 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. 2007;62:2635,Conclusions: Beta-blocker exposure was associated with a significant reduction in mortality in patients with
14、 severe TBI. 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 blunt head injury. J Am Coll Surg 2008; 206
15、: 432-38.,(metoprolol + clonidine)可以减轻血肿周围的水肿。,Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity After Brain Injury,治疗： -blockers + 2- agonists + morphine + baclofen + gabapentin 急性发作期：morphine + short-acting benzodiazepines A balance between control of symptoms without over sedation
16、is the goal.,Curr Neurol Neurosci Rep.2013V13N8 :370 J Neurosci Nurs.2016V48N2 :82-9,调查3000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内皮损伤,sympatho-adrenal hyperactivation,Endotheliopathy & capillary leakage (endothelial cell and glycocalyx damage),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！,Endogenous h
17、eparinization due to the shedding of the glycocalyx （syndecan-1）,内皮损伤的治疗：,Xu L, et al. Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy. Blood Coagul Fibrinolysis. 2015;26:15260. Chatterjee S, et al. Early intrave
18、nous beta-blockers in patients with acute coronary syndromea meta-analysis of randomized trials. Int J Cardiol. 2013;168(2):91521 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. 2013;310(16):168391.,intravenous beta-blockers +,Shangri-La的松赞林寺,Thanks for your attention!,