兒茶酚胺相關(guān)的毛細(xì)血管滲漏課件

1、Hello !兒茶酚胺相關(guān)的毛細(xì)血管滲漏1Hello !兒茶酚胺相關(guān)的毛細(xì)血管滲漏1兒茶酚胺相關(guān)的毛細(xì)血管滲漏許汪斌昆明醫(yī)科大學(xué)第一附屬醫(yī)院重癥醫(yī)學(xué)科兒茶酚胺相關(guān)的毛細(xì)血管滲漏2兒茶酚胺相關(guān)的毛細(xì)血管滲漏許汪斌兒茶酚胺相關(guān)的毛細(xì)血管滲漏2主要內(nèi)容：Case Report內(nèi)源性兒茶酚胺釋放/毛細(xì)血管滲漏Lund Concept之精髓Dexmedetomidine + Beta-blocker 兒茶酚胺相關(guān)的毛細(xì)血管滲漏3主要內(nèi)容：兒茶酚胺相關(guān)的毛細(xì)血管滲漏3Abel vanderschuren, et al. J. Neurosurg 110: 64-66. 200952歲的女性（Wt 50 k

2、g），既往無任何心血管疾病，左大腦前動(dòng)脈的動(dòng)脈瘤破裂，蛛網(wǎng)膜下腔出血（Fisher Grade 4 SAH），GCS 4分。入院后檢查：HR 115 bpm, ST, avL, V4-6 1 mm，QTc延長，心肌酶輕度升高（Troponin- 0.19 ng/mL），SBP從 125 mm Hg快速下降到80 mm Hg。急性肺水腫，肢端發(fā)冷，紫紺，給予經(jīng)口氣管插管，呼吸機(jī)支持，F(xiàn)iO2 0.6。嚴(yán)重的左心功能不全（心臟射血分?jǐn)?shù)18%），Swan-Ganz 導(dǎo)管監(jiān)測：CO 1.9 L/min, SvO2 44%。兒茶酚胺相關(guān)的毛細(xì)血管滲漏4Abel vanderschuren, et al.

3、 J. SAH所導(dǎo)致的心功能損傷兒茶酚胺相關(guān)的毛細(xì)血管滲漏5SAH所導(dǎo)致的心功能損傷兒茶酚胺相關(guān)的毛細(xì)血管滲漏5主要內(nèi)容：Case Report內(nèi)源性兒茶酚胺釋放/毛細(xì)血管滲漏Lund Concept之精髓Dexmedetomidine + Beta-blocker 兒茶酚胺相關(guān)的毛細(xì)血管滲漏6主要內(nèi)容：兒茶酚胺相關(guān)的毛細(xì)血管滲漏6重型顱腦損傷的病人，抽搐之后極易發(fā)生肺水腫（Neurogenic pulmonary edema）。SAH相關(guān)的心肌損傷（Stress-induced cardiomyopathy）。美軍越戰(zhàn)時(shí)期的醫(yī)療報(bào)告,合并有橫斷性頸脊髓受傷的顱腦創(chuàng)傷的士兵沒有肺水腫的發(fā)生。兒

4、茶酚胺相關(guān)的毛細(xì)血管滲漏7重型顱腦損傷的病人，抽搐之后極易發(fā)生肺水腫（Neurogen動(dòng)物實(shí)驗(yàn)：動(dòng)物實(shí)驗(yàn)顯示高顱壓可導(dǎo)致血漿的腎上腺素含量呈2001000倍的增加。去除支配心臟的交感神經(jīng)、或經(jīng)-阻滯劑預(yù)處理后，動(dòng)物的心臟可免于SAH所導(dǎo)致的損傷。臨床研究：SAH發(fā)病后盡快給予-阻滯劑(Labetalol)治療，有利于減輕應(yīng)激性心肌損傷的并發(fā)癥。血漿兒茶酚胺水平與顱腦創(chuàng)傷的死亡率有直接的相關(guān)性。Woolf PD, et al. The predictive value of catecholamines in assessing outcome in traumatic brain injury

5、. J neurosurg 1987; 66: 875-82.兒茶酚胺相關(guān)的毛細(xì)血管滲漏8動(dòng)物實(shí)驗(yàn)：Woolf PD, et al. The predSAH在發(fā)病后48小時(shí)內(nèi)血漿的去甲腎上腺素含量顯著增加并持續(xù)1周，血漿去甲腎上腺素含量回落到正常的水平需要6個(gè)月。兒茶酚胺相關(guān)的毛細(xì)血管滲漏9SAH在發(fā)病后48小時(shí)內(nèi)血漿的去甲腎上腺素含量顯著增加并持fluid and small solutesproteinfluid proteins and small solutesinterstitiumplasmasmall pore large pore DPDpDPDp=0Two-pore mode

6、l for fluid exchange by Rippe and Haraldsson, 1994Jv = KfPc - Pi兒茶酚胺相關(guān)的毛細(xì)血管滲漏10fluid and small solutesproteinControlNoradrenalin(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 246810

7、1214 (n=11)(n=11)By Per-Olof Grande（Rat with sepsis）Pc MAP兒茶酚胺相關(guān)的毛細(xì)血管滲漏11ControlNoradrenalin(n=11)(n=11重度顱腦損傷的兒茶酚胺風(fēng)暴（Catecholamine surge）：重度TBI的神經(jīng)重癥管理不僅應(yīng)重視繼發(fā)性腦損傷，還應(yīng)改善隨應(yīng)激反應(yīng)而激活的交感神經(jīng)所導(dǎo)致的毛細(xì)血管滲漏。大量的內(nèi)源性兒茶酚胺釋放全身性毛細(xì)血管滲漏低血容量災(zāi)難性低血壓兒茶酚胺相關(guān)的毛細(xì)血管滲漏12重度顱腦損傷的兒茶酚胺風(fēng)暴（Catecholamine su毛細(xì)血管滲漏的評(píng)估：昆明醫(yī)科大學(xué)第一附屬醫(yī)院重癥醫(yī)學(xué)科的方法：Alb

8、+ Alb/Glo(Hct - Alb )Xus index：（Hct 4045% Alb 35-50 g/L） Hct - Alb5兒茶酚胺相關(guān)的毛細(xì)血管滲漏13毛細(xì)血管滲漏的評(píng)估：Xus index：Hct - A毛細(xì)血管滲漏，大量的血漿蛋白外漏，血漿白蛋白（Albumin, Alb.）降低，伴隨血液的抽縮，血球壓積的增高（Haematocrit, Hct.）。（Hct - Alb）V RBC V Serum protein兒茶酚胺相關(guān)的毛細(xì)血管滲漏14毛細(xì)血管滲漏，大量的血漿蛋白外漏，血漿白蛋白（AlbumiQuantification of Capillary Leakage -By

9、Xus Index-HCT - ALB 5Hematocrit and plasma albumin levels difference may be a potential biomarker to discriminate preeclampsia and eclampsia in patients with hypertensive disorders of pregnancy . accepted in Clinica Chimica Acta in 1 Dec 2016.V RBC V Serum protein兒茶酚胺相關(guān)的毛細(xì)血管滲漏15Quantification of Cap

10、illary Le主要內(nèi)容：Case Report內(nèi)源性兒茶酚胺釋放/毛細(xì)血管滲漏Lund Concept之精髓Dexmedetomidine + Beta-blocker 兒茶酚胺相關(guān)的毛細(xì)血管滲漏16主要內(nèi)容：兒茶酚胺相關(guān)的毛細(xì)血管滲漏16Per-Olof Grnde缺氧所導(dǎo)致的細(xì)胞毒性水腫BBB損傷所導(dǎo)致的血管性水腫兒茶酚胺相關(guān)的毛細(xì)血管滲漏17Per-Olof Grnde缺氧所導(dǎo)致的細(xì)胞毒性水腫BBB兒茶酚胺相關(guān)的毛細(xì)血管滲漏18兒茶酚胺相關(guān)的毛細(xì)血管滲漏18兒茶酚胺相關(guān)的毛細(xì)血管滲漏19兒茶酚胺相關(guān)的毛細(xì)血管滲漏19兒茶酚胺相關(guān)的毛細(xì)血管滲漏20兒茶酚胺相關(guān)的毛細(xì)血管滲漏20Pc M

11、AP，血管性水腫兒茶酚胺相關(guān)的毛細(xì)血管滲漏21Pc MAP，血管性水腫兒茶酚胺相關(guān)的毛細(xì)血管滲漏21腦灌注壓腦血流量AA1A2腦血管自動(dòng)調(diào)節(jié)功能的損傷By Nordstrom CH.兒茶酚胺相關(guān)的毛細(xì)血管滲漏22腦灌注壓腦血流量AA1A2腦血管自動(dòng)調(diào)節(jié)功能的損傷By No腦灌注壓腦血流量AA1A2腦血管自動(dòng)調(diào)節(jié)功能的損傷piglet with TBIBy Nordstrom CH.兒茶酚胺相關(guān)的毛細(xì)血管滲漏23腦灌注壓腦血流量AA1A2腦血管自動(dòng)調(diào)節(jié)功能的損傷pigle腦灌注壓腦血流量AA1A2BC腦血管自動(dòng)調(diào)節(jié)功能的損傷piglet with bacterial meningitisBy N

12、ordstrom CH.兒茶酚胺相關(guān)的毛細(xì)血管滲漏24腦灌注壓腦血流量AA1A2BC腦血管自動(dòng)調(diào)節(jié)功能的損傷pigPc 1 mmHgICP 8 mmHg兒茶酚胺相關(guān)的毛細(xì)血管滲漏25Pc 1 mmHgICP 8 mmHg兒茶酚胺相關(guān)的毛細(xì)血Intracranial pressure (mmHg)baselineElevated blood pressureBaseline blood pressurebaselineElevated blood pressureElevated blood pressureBaseline blood pressureEffects of increase i

13、n blood pressure (30 mmHg) on ICPBy Per-Olof Grande（cat with bacterial meningitis）兒茶酚胺相關(guān)的毛細(xì)血管滲漏26Intracranial pressure (mmHg)ba腦灌注壓腦血流量AA1A2BCLund concept for CPP in TBI CPP 70 mm HgCPP 5060 mm Hg兒茶酚胺相關(guān)的毛細(xì)血管滲漏27腦灌注壓腦血流量AA1A2BCLund concept foPer-Olof Grnde缺氧所導(dǎo)致的細(xì)胞毒性水腫BBB損傷所導(dǎo)致的血管性水腫兒茶酚胺相關(guān)的毛細(xì)血管滲漏28Per-

14、Olof Grnde缺氧所導(dǎo)致的細(xì)胞毒性水腫BBBQ = CPP/R問題的提出：誰對(duì)損傷區(qū)域血流灌注的影響最大？兒茶酚胺相關(guān)的毛細(xì)血管滲漏29Q = CPP/R兒茶酚胺相關(guān)的毛細(xì)血管滲漏29R CPP兒茶酚胺相關(guān)的毛細(xì)血管滲漏30R CPP兒茶酚胺相關(guān)的毛細(xì)血管滲漏30縮血管藥物（VASOCONSTRICTORS） have adverse effects not only by compromising circulation of the penumbra zone, but also by increasing the loss of plasma to the interstitium

15、兒茶酚胺相關(guān)的毛細(xì)血管滲漏31縮血管藥物（VASOCONSTRICTORS） have Avoid Stress and hyperventilation as they both may induce vasoconstriction of the penumbra zonesevere head injury兒茶酚胺相關(guān)的毛細(xì)血管滲漏32Avoid Stress and hyperventilat降低機(jī)體的應(yīng)激反應(yīng)/內(nèi)源性兒茶酚胺釋放:在顱腦創(chuàng)傷病人還未轉(zhuǎn)入ICU之前，就應(yīng)主動(dòng)的給予鎮(zhèn)靜鎮(zhèn)痛的治療（安定類藥物 + 阿片類藥物），以有效的降低機(jī)體的應(yīng)激反應(yīng)。轉(zhuǎn)入ICU之后，進(jìn)一步的降低機(jī)體的

16、應(yīng)激反應(yīng)，以及體內(nèi)的兒茶酚胺的釋放，給予咪唑安定 + 芬太尼 + 1受體阻斷劑美托洛爾 + 2受體激動(dòng)劑可樂定。 兒茶酚胺相關(guān)的毛細(xì)血管滲漏33降低機(jī)體的應(yīng)激反應(yīng)/內(nèi)源性兒茶酚胺釋放:兒茶酚胺相關(guān)的毛細(xì)血降低腦毛細(xì)血管的靜水壓+ 抗應(yīng)激：1受體拮抗劑美托洛爾+ 中樞性的2激動(dòng)劑可樂定 維持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

17、 in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology 98, 809-814.兒茶酚胺相關(guān)的毛細(xì)血管滲漏34降低腦毛細(xì)血管的靜水壓+ 抗應(yīng)激：兒茶酚胺相關(guān)的毛細(xì)血管滲漏主要內(nèi)容：Case Report內(nèi)源性兒茶酚胺釋放/毛細(xì)血管滲漏Lund Concept之精髓Dexmedetomidine + Beta-blocker 兒茶酚胺相關(guān)的毛細(xì)血管滲漏35主要內(nèi)容：兒茶酚胺相關(guān)的毛細(xì)血管滲漏35J Trauma. 2007;62:2635兒茶酚胺相關(guān)的毛細(xì)血管滲漏36

18、J Trauma. 2007;62:2635兒茶酚胺相關(guān)的兒茶酚胺相關(guān)的毛細(xì)血管滲漏37兒茶酚胺相關(guān)的毛細(xì)血管滲漏37兒茶酚胺相關(guān)的毛細(xì)血管滲漏38兒茶酚胺相關(guān)的毛細(xì)血管滲漏38兒茶酚胺相關(guān)的毛細(xì)血管滲漏39兒茶酚胺相關(guān)的毛細(xì)血管滲漏39Conclusions: Beta-blocker exposure was associated with a significant reduction in mortality in patients with severe TBI. This reduction in mortality is even more impressive, conside

19、ring that the BB(+) group was older, more severely injured, and had lower predicted survival.兒茶酚胺相關(guān)的毛細(xì)血管滲漏40Conclusions: 兒茶酚胺相關(guān)的毛細(xì)血管滲漏40NICU救治年齡55歲的重型顱腦創(chuàng)傷，給予1受體阻劑的治療，死亡率從60%降致28%。Kenji Inaba, et al. Beta-Blockers in isolated blunt head injury. J Am Coll Surg 2008; 206: 432-38.兒茶酚胺相關(guān)的毛細(xì)血管滲漏41NICU救治年齡

20、55歲的重型顱腦創(chuàng)傷，給予1受體阻劑的(metoprolol + clonidine)可以減輕血腫周圍的水腫。兒茶酚胺相關(guān)的毛細(xì)血管滲漏42(metoprolol + clonidine)可以減輕血腫Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity After Brain Injury治療： -blockers + 2- agonists + morphine + baclofen + gabapentin急性發(fā)作期：morphine + short-acting benzodiazepinesA balance

21、between control of symptoms without over sedation is the goal.Curr Neurol Neurosci Rep.2013V13N8 :370J Neurosci Nurs.2016V48N2 :82-9 兒茶酚胺相關(guān)的毛細(xì)血管滲漏43Pharmacologic Management of Pa調(diào)查3000例患者（創(chuàng)傷、膿毒癥、心梗、心臟驟停后綜合征），發(fā)現(xiàn)具有共同的病理生理改變內(nèi)皮損傷兒茶酚胺相關(guān)的毛細(xì)血管滲漏44調(diào)查3000例患者（創(chuàng)傷、膿毒癥、心梗、心臟驟停后綜合征），sympatho-adrenal hyperactivationEndotheliopathy & capillary leakage (endothelial cell and glycocalyx damage)兒茶酚胺相關(guān)的毛細(xì)血管滲漏45sympatho-adrenal hyperactivati內(nèi)皮損傷的程度與兒茶酚胺的濃度成正比！毛細(xì)血管滲漏和凝血功能紊亂是內(nèi)皮損傷最終結(jié)果！Endogenous heparinization due to the shedding of the glycocalyx （syndecan-1）兒茶酚胺相關(guān)的毛細(xì)血管滲漏46內(nèi)皮損傷的