1、专用术语说明,肺循环高压（Pulmonary hypertension）整个肺循环，任何系统或者局部病变而引起肺循环血压增高。包括：肺动脉高压、肺静脉高压、混合性肺动脉高压。 肺动脉高压（Pulmonary arterial hypertension）肺动脉压力增高, 而肺静脉压力正常 特发性肺动脉高压 (Idiopathic Pulmonary arterial hypertension)无任何原因（遗传、病毒、药物等）发生的肺动脉高压,Definition,正常人肺动脉压力为1530/510mmHg，平均为15 mmHg。 静息状态下，若肺动脉收缩压30 mmHg，或平均压20 mmHg，
2、即为肺动脉高压。 WHO规定：海平面状态下，静息时，右心导管检查肺动脉收缩压30 mmHg，和/或肺动脉平均压25 mmHg，或运动时肺动脉平均压30 mmHg，即为肺循环高压。诊断肺动脉高压，尚需PCWP 15 mmHg,Severity of Pulmonary Hypertension,Degree of disease Mild Moderate Severe,Mean PAP (mmHg) 20 - 30 30 - 50 50,Classification of Pulmonary Hypertension,1975 WHO Classification Primary pulmon
3、ary hypertension (PPH) Secondary pulmonary hypertension 1998 Evian Classification Clinical classification system Different categories sharing similarities in pathophysiological mechanisms, clinical presentations, therapeutic options 2003 Revised Clinical Classification of Pulmonary Hypertension,Clin
4、ical Classification of Pulmonary Hypertension,Venice 2003,Evian 1998,WHO肺动脉高压患者功能分级,Mechanisms of pulmonary hypertension,肺动脉高压的细胞机制 肺血管结构重构是肺动脉高压重要的病理基础 内皮细胞、平滑肌细胞、成纤维细胞、血小板和血栓形成、炎症细胞,Mechanisms of pulmonary hypertension,肺动脉高压的分子机制多种血管活性物质，正常情况下它们之间处于动态平衡，维持肺血管的正常生理结构和功能 气体信号分子 NO 、CO、 H2S血管活性肽及其他血管
5、活性物质 依前列醇(前列环素，eroprostenol，prostacyclin，PGI2) 肾上腺髓质素(ADM) 内皮素-1(endothelin一1，ET一1)： 血管紧张素 5一羟色胺(5一HT ) 血管活性肠肽 钾通道,Injury to endothelial cells leads to overproduction of endothelin key cause of blood vessel scarring and spasm & to reduced production of nitric oxide and prostacyclins 2 key body chemi
6、cals which keep blood vessels relaxed and open.,肾上腺髓质素(ADM),ADM 是1993年由日本学者在嗜铬细胞瘤中发现的一种新型血管活性多肽 具有舒张血管、降低血压、利尿排钠和抑制血管平滑肌迁移增殖等多种生物学作用。 持续给予低氧大鼠ADM，能够缓解肺血管结构重构和肺动脉高压的形成,5-HT in pulmonary hypertension MacLean (1999) TIPS 20:490,Blood vessel alveolar lumen,K+ channel abnormalities in Primary PH (PPH) Ar
7、cher & Rich (2000) Circulation 102:2782,Decreased Kv1.5 in PPH Impaired K+ current in PPH,SPH secondary PH Donor and NPH- normals,Mechanisms of pulmonary hypertension,肺动脉高压的遗传机制 IPAH为常染色体显性遗传，但是不完全外显，相关突变的携带者中只有10 20有明显的肺动脉高压表 目前认为骨形成蛋白型受体(bone morphogenetic protein receptor II，BMPR2) 基因突变是IPAH的重要致病
8、原因,According to the hypothesis, vascular abnormalities characteristic of PPH are triggered by accumulation of genetic and/or environmental insults in a susceptible individual. A combination of germline BMPR2 mutation (first hit) and the ingestion of appetite suppressants (second hit) were used to ge
9、nerate the clinical disease.,WHAT IS PH?,MECHANISMS OF PH,TREATMENT OF PH,Pathophysiology,Acute: RV afterload, EDV, EF, SV of RV Chronic: progressive systolic pressure overload of RV that dilates and hypertrophies, gradual RV dysfunction venous return compromises RV preload and pulm blood flow resul
10、ts from positive intrathoracic pressure (ex. PEEP) which also causes alveolar overdistension which PVR and pulm blood flow,Pathophysiology,-PVR limits RV SV and the volume for LV filling -LV compressed by intraventricular septum during systole, LV volume/filling, CO/BP -BP leads to coronary perfusio
11、n which can lead to myocardial ischemia/R sided failure -coronary blood flow to RV usually occurs during diastole and systole but is decreased if RV pressures are equal to or higher than systemic pressures -hypoxemia from CO/pulm blood flow or from R to L intracardiac shunt (if RA pressures higher t
12、han LA),Signs of Disease Severity,Dyspnea at rest Low cardiac output with metabolic acidosis Hypoxemia Signs of right heart failure (large V wave on jugularis vein, periph edema, hepatomegaly) Syncope (poor prognosis) Chest pain (RV ischemia),Physical Exam,Loud P2 (increases PAP) Left parasternal he
13、ave (R sided overload) Pulm valve regurgitation (dilatation of pulm valve annulus) S3 gallop (advanced RV failure),Recommended Tests before Anesthesia,ECG: RV/RA enlargement CXR: enlarged central and R/L pulmonary arteries, cardiac silhouette ABG ECHO: ? TR, ?PFO, estimation of pulm pressure, RV hyp
14、ertrophy, dilatation of RV with impairment of LV filling, paradoxical mvmt of IV septum Cardiac Catheterization: pulm pressures, CO, response to vasodilators, ?PFO, status of coronary circulation,Anesthetic Considerations: Pre-op,Maintain all pulm vasodilators ex. prostacyclin, Ca2+ antagonists, pho
15、sphodiesterase-5-inhibitors (sildenafil, dypiridamole), endothelin receptor antagonists (Bosentan) and O2 If pulm HTN diagnosed immediately pre-op and OR cant be delayed, start sildenafil (0.1mg/kg daily up to 0.5mg/kg q6hrs, adults 50-100mg daily, IV 0.2mg/kg/hr) and l-arginine (15gm daily) if clin
16、ical signs of pulm HTN or poor ex tolerance Heparin should replace indirect anticoagulant (ie. Coumadin) until OR Premed: slight midaz OK as long as resp acidosis/BP not induced,Anesthetic Considerations: Goals,Maintain NSR Avoid tachycardia Avoid hypotension/hypertension Avoid all factors that incr
17、ease PVR: Hypoxia Hypercarbia Acidosis Pain/noxious stimuli Low lung volumes/overdistension,Anesthetic Considerations: Induction,Few studies showing effect on vasoreactivity Opioids used at a dose to block the cardioresp response of intubation, they have no direct effect on pulm vessels Lidocaine (1
18、mg/kg) can help suppress response to intubation Propofol, pentothal or etomidate may be used Depolarizing or nondepolarizing muscle relaxants could be used (avoid MR releasing histamine),Anesthetic Considerations: Maintenance,Volatiles (iso-most common, des, sevo) can be used Desflurane Potentiates
19、pulm vasoconstriction to adrenoceptor activation Isoflurane Attenuates magnitude of hypoxic pulm vasoconstriction Potentiates vasodilator response to B1 adrenoceptor activation No effect on alpha 1 vasoconstriction Maintain opioids at a surgical analgesic level Maintain muscle relaxation,Monitoring,
20、Art line CVP or PAC TEE if available,Treatment of Pulm HTN During Surgery,Inhaled NO (20-40 ppm) Milrinone (50ug/kg bolus then 0.5-0.75ug/kg/min) Dypiridamole (0.2-0.6 mg/kg IV over 15min q 12hrs) Inhaled prostacyclin (nebulized or IV 2-20 mcg/kg/min) Mg: smooth muscle relaxant, attenuates the effec
21、t of hypoxia on PVR (serum conc 3-5mmol/L),Nitric Oxide,Selective pulmonary vasodilation, improves oxygenation cGMP Used in ARDS, PPHN, cardiogenic shock, post CPB Risks: methemoglobinemia and carboxyhemoglobinemia, rebound pulm HTN when stopped Requires closed inhalational circuit,Phosphodiesterase
22、 inhibitors,Inhibition of nitric oxide degradation Sildenafil (PDE-5 inhibitor): PAP/PVR Min effects on systemic vasculature Synergistic with NO Reduction in RV mass: role in prevention or reversal of remodeling of RV Milrinone (PDE-3 inhibitor): PVR/PAP/SVR in setting of CV shock Nebulized minimize
23、s systemic vasodilation,Prostacyclins,Potent pulm and systemic vasodilators with antiplatelet properties Epoprostenol (IV): PVR, better CO/ex. Tolerance s/e: BP, need for central line (risk of infection) Beraprost (PO): Longer duration Iloprost (nebulized),Endothelin receptor antagonists,Endothelin-
24、1: neurohormone that causes pulm vasoconstriction, smooth muscle proliferation, fibrosis Stimulates endothelin receptors A & B A: vasconstriction B: vasodilation Nonselective: Bosentan A selective: sitaxsentans/e: hepatic toxicity,Ca channel blockers,Chronic pulm HTN Rx s/e: hypotension causing refl
25、ex tachycardia Only 15-25% of pts respond Need to undergo vasoreactivity testing prior to starting,Post-op,ICU Optimal analgesia with continuous epidural, regional block or parenteral opioids Avoid, hypoxemia, BP, hypovolemia Risk of acute pulm vasospasm, arrhythmia, fluid shifts, sympathetic tone,
26、pulm vasc tone Wean any pulmonary vasodilators progressively,麻醉医师围术期工作,正确评估肺高压及肺血管病变的可逆程度 围术期肺的保护 预防和避免引起/加重肺高压的因素 针对肺高压、右心衰治疗,正确评估肺高压及肺血管病变,评估目的：对肺高压中可逆和不可逆的两种成分比重进行判断 方法：用一系列肺血管扩张药物治疗后，进行重复、动态地肺循环参数测定来识别肺高压中可逆和不可逆的两种成分的比重,肺动脉高压严重程度的评估,肺动脉压：PADP越高肺血管阻力越大（肺、主动脉瓣关闭不全时，不能反映） 肺/体血流比值：3时，无明显肺血管阻力升高 肺动脉血
27、氧饱和度：较好反映肺血流和PVR 吸氧反应及血管扩张药物反应 肺活检：估计肺血管病变的性质和程度,血管扩张试验,方法：吸入NO1020ppm,10min 吸入依洛前列素810ug,15min IV前列环素2ng/(kg.min)并逐渐增加至不能耐受，30min IV腺苷50ug/(kg.min)并逐渐增加至不能耐受，10min 试验阳性定义（欧洲心脏协会）：mPAP至少降低10mmHg,并且绝对值 40mmHg，伴CO增加或不变,针对肺高压右心衰治疗,基本治疗 提高吸氧浓度改善缺氧 过渡通气，保持PaCO2在30-35mmHg,避免呼酸 纠正代酸 加强呼吸管理，避免Q/V失调 适当镇静、镇痛，
28、避免过度应激导致EA释放 维持体温37，避免寒战,针对肺高压右心衰治疗,特殊处理 降低右室后负荷 血管扩张药 维持和支持心肌收缩 儿茶酚胺类正性肌力药 磷酸二酯酶抑制剂 增加右冠灌注压 1受体激动药苯肾上腺素,钙离子拮抗试剂 前列环素类药物 内皮素受体拮抗剂 5型磷酸二酯酶抑制剂 NO 联合治疗,血管扩张药,静脉注射血管扩张药物的副作用,体循环血管扩张致低血压冠脉灌注减少导致并加重右心衰 Q/V失调，加重低氧血症,弥补方法,采用选择性扩张肺动脉的药物 改变用药途径 吸入法代替静脉给药 代表药物：一氧化氮（Nitric Oxid） 依洛前列素（IIoprost） 西地那非（Sildenafil） 双心给药：肺动脉给扩血管药，同时经左心给缩血管药,THANK YOU FOR YOUR ATTENTION!AND HAVE A PLEASANT DAY!,
