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1、 Hello ! 兒茶酚胺相關(guān) 的毛細血管滲漏 許汪斌 昆明醫(yī)科大學第一附屬醫(yī)院重癥醫(yī)學科 主要內(nèi)容: Case Report 內(nèi)源性兒茶酚胺釋放 /毛細血管滲漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker Abel vanderschuren, et al. J. Neurosurg 110: 64-66. 2009 52歲的女性( Wt 50 kg),既往無任何心血管疾病,左大腦前動脈的 動脈瘤破裂,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
2、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,呼吸機支持, FiO2 0.6。 嚴重的左心功能不全(心臟射血分數(shù) 18%), Swan-Ganz 導管監(jiān)測: CO 1.9 L/min, SvO2 44%。 SAH所導致的心功能損傷 主要內(nèi)容: Case Report 內(nèi)源性兒茶酚胺釋放 /毛細血管滲漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker 重型顱腦損傷的病人,抽搐之后極易發(fā)生肺水腫 ( N
3、eurogenic pulmonary edema)。 SAH相關(guān)的心肌損傷( Stress-induced cardiomyopathy)。 美軍越戰(zhàn)時期的醫(yī)療報告 ,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。 動物實驗: 動物實驗顯示高顱壓可導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) -阻滯劑預處理后,動物的心臟 可免于 SAH所導致的損傷。 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 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.
4、 The predictive value of catecholamines in assessing outcome in traumatic brain injury. J neurosurg 1987; 66: 875-82. SAH在發(fā)病后 48小時內(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個月。 fluid and small solutes protein fluid proteins and small solutes interstitium plasma small pore large pore DP Dp DP Dp=0
5、 Two-pore model for fluid exchange by Rippe 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
6、) By Per-Olof Grande ( Rat with sepsis) Pc MAP 重度顱腦損傷的兒茶酚胺風暴( Catecholamine surge) : 重度 TBI的神經(jīng)重癥管理不僅應重視繼發(fā)性腦損傷,還應改善隨 應激反應而激活的交感神經(jīng)所導致的毛細血管滲漏。 大量的內(nèi)源性兒茶酚胺釋放 全身性毛細血管滲漏 低血容量 災難性低血壓 毛細血管滲漏的評估: 昆明醫(yī)科大學第一附屬醫(yī)院重癥醫(yī)學科的方法 : Alb+ Alb/Glo (Hct - Alb ) Xus index: ( Hct 4045% Alb 35-50 g/L) Hct - Alb 5 毛細血管滲漏,大量的血漿蛋白外
7、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 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
8、hypertensive disorders of pregnancy . accepted in Clinica Chimica Acta in 1 Dec 2016. V RBC V Serum protein 主要內(nèi)容: Case Report 內(nèi)源性兒茶酚胺釋放 /毛細血管滲漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker Per-Olof Grnde 缺氧所導致的細胞毒性水腫 BBB損傷所導致的血管性水腫 Pc MAP, 血管性水腫 腦灌注壓 腦血流量 A A1 A2 腦血管自動調(diào)節(jié)功能的損傷 By Nordstrom CH. 腦灌注壓
9、 腦血流量 A A1 A2 腦血管自動調(diào)節(jié)功能的損傷 piglet with TBI By Nordstrom CH. 腦灌注壓 腦血流量 A A1 A2 B C 腦血管自動調(diào)節(jié)功能的損傷 piglet with bacterial meningitis By Nordstrom CH. Pc 1 mmHg ICP 8 mmHg Intracra nial pre ssure (mm Hg ) ba se lin e Elev ated bloo d pressu re Ba se lin e bloo d pressu re ba se lin e Elev ate d b loo d pr
10、essu re Elev ate d b loo d pressu re Ba se lin e b loo d pressu re Effects of increase in blood pressure (30 mmHg) on ICP By Per-Olof Grande ( cat with bacterial meningitis) 腦灌注壓 腦血流量 A A1 A2 B C Lund concept for CPP in TBI CPP 70 mm Hg CPP 5060 mm Hg Per-Olof Grnde 缺氧所導致的細胞毒性水腫 BBB損傷所導致的血管性水腫 Q = C
11、PP/R 問題 的提出: 誰對損傷區(qū)域血流灌注的影響最大? R CPP 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 Avoid Stress and hyperventilation as they both may induce vasoconstriction of the penumbra zone
12、severe head injury 降低機體的應激反應 /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,就應主動的給予鎮(zhèn)靜鎮(zhèn)痛 的治療(安定類藥物 + 阿片類藥物),以有效的降低機體的 應激反應。 轉(zhuǎn)入 ICU之后,進一步的降低機體的應激反應,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受體激動劑可樂定。 降低腦毛細血管的靜水壓 + 抗應激: 1受體拮抗劑美托洛爾 + 中樞性的 2激動劑可樂定 維持 CPP 5060 mm Hg (metoprolol + clonidine) NORDSTROM, C.H., REINSTRUP,
13、P., XU, W., et al.(2003). Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology 98, 809-814. 主要內(nèi)容: Case Report 內(nèi)源性兒茶酚胺釋放 /毛細血管滲漏 Lund Concept之精髓 Dexmedetomidine + Beta-blocker J Trauma. 2007;62:2635 C
14、onclusions: 1. Beta-blocker exposure was associated with a significant reduction 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救治年齡 55歲的重型顱腦創(chuàng)傷,
15、 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. 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-
16、acting benzodiazepines A balance between control of symptoms without over sedation is the goal. Curr Neurol Neurosci Rep.2013V13N8 :370 J Neurosci Nurs.2016V48N2 :82-9 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 Shock trauma sepsis Myocardial infarction (MI) post cardiac arrest syndrome (PCAS
17、) sympatho-adrenal hyperactivation Endotheliopathy 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. 2013;168(2):91521 3. 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的松贊林寺 Thanks for your attention!