1、 讲述内容讲述内容1 背景2 靶向治疗思路来源-来自循征医学3 总体原则-来自个体认识4 具体实施方案-循征+个体5 效果评价讲课内容一讲课内容一背景背景中国孕产妇.围产儿死亡情况20132013年：年：23.2/1023.2/10万万20132013年：婴儿死亡率，年：婴儿死亡率，9.59.5近年来呈上升趋势，全球范围内近年来呈上升趋势，全球范围内1400万发生率，每万发生率，每4分钟分钟1例死亡例死亡 因素因素 /1000 OR aORJ Obstet Gynaecol Can 2014;36(1):2133妊娠仍然是导致生育年龄妇女死亡主要原因International Journal
2、of Womens Health 2014:6 4146可避免死亡原因分类CoastalInlandRemoteCoastalInlandRemote1996-2000PPH84(34.71)84(34.71)317(48.40)317(48.40)364(59.19)364(59.19)7.377.3725.6225.6271.7371.73PE35(14.46)94(14.35)82(13.33)3.077.6016.16AFE32(13.22)41(6.26)12(1.95)2.813.312.36Cardiac disorders32(13.22)63(9.62)37(6.02)2.8
3、15.097.29Puerperal infection4(1.65)24(3.66)43(6.99)0.351.948.47Hepatic diseases13(5.37)17(2.60)12(1.95)1.141.372.362001-2005PPH72(51.80)72(51.80)268(50.85)268(50.85)196(54.14)196(54.14)6.976.9721.8821.88* * *40.0140.01* * *PE18(12.95)70(13.28)50(13.81)1.74*5.72*10.21AFE14(10.07)32(6.07)16(4.42)1.362
4、.613.27Cardiac disorders6(4.32)54(10.25)31(8.56)0.58*4.416.33Puerperal infection1(0.72)18(3.42)17(4.70)0.101.473.47*Hepatic diseases2(1.44)10(1.90)7(1.93)0.190.821.43可避免死亡比例可避免死亡比例疾病至死疾病至死各级医院业务水平ProblemsCoastalInlandRemoteFor individual/family143(37.54)523(44.24)651(66.70)Knowledge/skill108(28.35)3
5、51(29.69)450(46.11)Attitude26(6.83)110(9.30)97(9.94)Resources9(2.36)62(5.25)104 (10.66)For medical institutions237(62.19)635(53.74)305(31.25)Knowledge/skill223(58.52)591(50.01)289(29.61)Village-level21(5.51)197(16.67)100(10.25)Township-level73(19.16)167(14.13)73(7.48)County-level79(20.73)160(13.54)8
6、2(8.40)Province-level50(13.12)67(5.67)34(3.48)For social departments1(0.27)24(2.02)20(2.05)Knowledge/skill0(0.00)14(1.18)4(0.41)Attitude0(0.00)2(0.17)0(0.00)Management0(0.00)2(0.17)11(1.13)Resources1(0.27)6(0.50)5(0.50)产后出血诊治中存在问题诊断错误或延迟诊断诊断错误或延迟诊断缺乏产后出血共识低估出血速度与出血量缺乏医院内ease-use action plans缺乏足够的培训（
7、理论+技能）治疗效果差加强子宫收缩药物使用不当输注血液制品延迟（红细胞、凝血制剂）忽略了最基本监测结果治疗决策失误组织系统不完善设备、人员、交通、技术、合作Too little is done “too late “产后出血定义问题产后出血产后出血严重产后出血严重产后出血传统定义：传统定义： 阴道分娩-500mml transfusion 4units of blood 剖宫产-1000mml 3小内失血超过血容量 50%澳大利亚（澳大利亚（2008年）年） 20分钟内失血 150ml/ (50% blood volume)出血-500-1000mml伴有低血容量休克 外周血血红蛋白浓度降低4
8、0g/l或失血-1000mml sudden blood loss 1500ml (25% of the blood volumeRCOG（2009年）失血-500-1000mml不伴有低血容量休克严重出血-1000mml -轻度-1000-2000mml -重度-1000mml能反映临床问题吗？能反映临床问题吗？产科危急重症患者管理产科危急重症患者管理1010大不足大不足-我们医院？我们医院？1缺乏监护设备缺乏监护设备-以往主要放置在以往主要放置在ICU2重症病房设备仅提供生命体征3监护间隔时间过长，未根据患者病情进行调整，且不完整4护士巡视患者间隔时间过长5医师巡视过少，每天1次6非特异性
9、生命体征变化未进行规范化处置7重症患者单一医师处置（经验性处置）8危急重症患者团队组织时间过长9医师.护士人员不足10现代医院管理缺陷内容二.开展产后出血治疗-理论基础.实践失血性休克发生严重并发症机制？失血性休克发生严重并发症机制？治疗靶点治疗靶点治疗靶点治疗靶点控制失血控制失血容量补充容量补充并发症预防并发症预防Reduction in maternal mortality requires an in-depth knowledge of the causes of death 失血性休克患者死亡Korean J Anesthesiol. 2011 March; 60(3): 15116
10、0内容三.靶向治疗临床实践：控制出血产后出血治疗产后出血治疗-时刻准备时刻准备.演练演练16初始治疗初始治疗难治性产后出血难治性产后出血MODs患者死亡患者死亡快速反应团队快速反应团队三衰治疗小组三衰治疗小组.ICU具体止血措施-原因处置（产科医师能做到的？）一线治疗方案一线治疗方案加强子宫收缩药物加强子宫收缩药物子宫按摩子宫按摩排空膀胱排空膀胱软产道损伤缝合软产道损伤缝合残留胎盘处置残留胎盘处置水囊压迫水囊压迫二线治疗方案二线治疗方案子宫缝扎子宫缝扎-82-100%82-100%子宫血管结扎（髂内等）子宫血管结扎（髂内等）双侧双侧80-96%80-96% 单侧单侧42-93%42-93%子宫
11、动脉栓塞子宫动脉栓塞- -70-100%-70-100%-子宫收缩乏力子宫收缩乏力 60-83%-60-83%-胎盘植入胎盘植入三线治疗三线治疗子宫切除子宫切除-94-99%-94-99% 全子宫切除全子宫切除 次全子宫切除次全子宫切除A/B/C/D/E|F管理管理产科医师至少应掌握技术：缩宫素使用、缝扎技术、球囊使用、子宫切除产科医师至少应掌握技术：缩宫素使用、缝扎技术、球囊使用、子宫切除必要时：必要时：aortic cross-clamping预防与治疗产科出血药物与措施加强子宫收缩预防与治疗性药物，缩宫素加强子宫收缩预防与治疗性药物，缩宫素. .前列腺素前列腺素. .麦角新碱麦角新碱注意
12、点1.出血性休克患者止血-早期干预 We recommend that patients presenting with haemorrhagic shock and an identified source of bleeding undergo an immediate bleeding controlprocedure unless initial resuscitation measures are successful (Grade 1B)三要三要- -止血止血要要迅速迅速. .措施措施要要有综合有综合. . 效果效果要要有效有效三防三防-单独救治单独救治. .不个体化不个体化. .
13、没有准备与培训没有准备与培训Time to hemostasis（药物（药物+栓塞栓塞+手术）手术）(Grade 1C) Every 3 minutes of delay in the resuscita-tion room leads to a 1% mortality increase in a patient with hemodynamic instability and blunt abdominal trauma during the first 90 minutes of treatment at a Level I trauma center死亡三角：低体温死亡三角：低体温.
14、.凝血功能障碍凝血功能障碍. .酸中毒酸中毒处置措施、止血速度对患者结局影响较大注意点3.栓塞治疗疗不能解决出血中的所有问题J. Perinat. Med. 2014; 42(3): 359362止血时间对患者结局影响注意点4.简单有效处置方法还在培训.使用吗？J. Obstet. Gynaecol. Res. 2011, 11: 15571563注意点5.产后出血诊断方法不能满足临床需求（容积法、面积法、称重法）2000mml2000mml液体快速输注患者变化液体快速输注患者变化（1）腹主动脉阻断）腹主动脉阻断. In the exsanguinating patient, aortic c
15、ross-clamping may be employed as an adjunct (Grade 1C)注意点注意点6. 产后出血处理还有进一步措施产后出血处理还有进一步措施（2）. 损伤控制性手术：损伤控制性手术： deep haemorrhagic shock, signs of ongoing bleeding and coagulopathy. hypothermia, acidosis, inaccessible major anatomical injury, a need for time-consuming procedures or concomitant major i
16、njury outside the abdomen (Grade 1C).（3 3）出血局部用药）出血局部用药注意点7：体温维持early application of measures to reduce heat loss and warm the hypothermicpatient in order to achieve and maintain normothermia (Grade 1C)体温J Trauma Acute Care Surg ，3, （6）, Supplement 5低体温影响低体温影响内容四.容量补充何时？何时？ 怎样？怎样？ 均牵涉失血量估计均牵涉失血量估计多少
17、？多少？1.出血量估计4 4个个100100方案方案-失血量估计失血量估计血压100次/分钟，尿量100X10mml广州孕产妇救治中心广州孕产妇救治中心根据出血量及临床表现进行分度1grade I (blood loss 1- 1-休克休克 1.5-1.5-严重休克，失血严重休克，失血30%30%50%50% 2- 2-重度休克，失血重度休克，失血50%50%丢失血容量计算 血液稀释法，抽出的血容量（血液稀释法，抽出的血容量（V V）或最佳初期血细胞比容（）或最佳初期血细胞比容（HctHct）可由以）可由以下公式算出：下公式算出： V=EBVV=EBV (Hct(Hcti i HctHctf
18、f)/Hct)/Hctav av （EBVEBV是估计血容量、是估计血容量、HctHctf f是最低血细胞比容、是最低血细胞比容、HctHctavav是平均血细胞比容是平均血细胞比容 (Hct(Hcti i HctHctf f)/2)/2）注意点：HCT受诸多因素影响We do not recommend the use of single Hct measurements as an isolated laboratory marker for bleeding (Grade 1B）2.补充血容量.About time 1. definition of haemorrhagic shock
19、, (SBP 90 mmHg and BE -6 mmol/l), 2. expected and ongoing bleeding (not meeting haemorrhagic shock criteria, but with either prehospital blood loss and/or expected further blood loss intraoperatively due to the need for multiple procedures) 3. dropping Hb (Hb drop to below 80 g/l or below 100 g/l an
20、d 30 g/l drop within 2 h 4. low SBP (persistent hypotension on serial measurements 110 beats/min for at least 30 min despite fluid replacement) 注意点.so-called permissive hypotension target systolic blood pressure of 80 to 100 mmHg until major bleeding has been stopped in the initial phase following t
21、rauma (Grade 1C) Coagulopathy wasobserved in more than 40% of patients with more than 2000 ml, in more than 50% with more than 3000 ml, and in more than 70% with more than 4000 ml administered Several experimental studies have shown that maintaining an SBP of approximately 90 mm Hg and an MAP around
22、 60 mm Hg, until definitive surgical hemostasis was achieved, resulted in increased oxygen delivery,decreased blood loss, and reduced mortality A strategy that accepts a certain degree of hypotension in order to balance the primary of goal of organ perfusion against the risks of rebleeding that may
23、develop with resuscitation to a normotensive state注意点.Fluid therapyCrystalloids（晶体液）（晶体液） be applied initially to treat the bleeding trauma patient (Grade 1B)hypertonic solutions also be considered during initial treatment (Grade 2B). the addition of colloids be considered within the prescribed limi
24、ts for each solution in haemodynamicallyunstable patients (Grade 2C)注意点.液体量-反思与争议1.1.初期：来自动物实验结果，初期：来自动物实验结果，3:13:1液体补充疗法，液体补充疗法，越战期间：未控制性出血的限制性补液越战期间：未控制性出血的限制性补液2. demonstrated that a 2 L crystalloid bolus administered before intrinsic hemostasis was achieved, increased blood loss from 4% to 29%，F
25、urthermore, that same 2 Lcrystalloid bolus administered at a high rate (0.2 L/min)did not even transiently correct the existing hypotension in a patient that has lost blood at a rate of 1.5 L in 15 minutes and still has ongoing bleeding. Further, this high volume and rate of crystalloids carried a h
26、igh probability of triggering rebleeding if administered to a patient during the period when the initial thrombus was forming (usually within the first 30 min of injury).3. Acute hemorrhage (30% total estimated blood volume) caused a rapid andmoderate drop in mean Hct to 17% below baseline within 15
27、 minutes posthemorrhage. Large-volume fluid resuscitation (3:1) resulted in a further Hct drop to 50% below baseline, whereas small-volume resuscitation (1:1) resulted in a decrease in Hct to only 24% below baseline. In addition, large-volume resuscitation resulted in amore significant prolongation
28、of the prothrombin time and decrease in platelet count as compared to small- volume resuscitation. Interestingly, although large-volume resuscitation resulted in a supranormal elevation of cardiac output initially, this effect was only transient (approximately 30 min) and overall there was no sustai
29、ned advantage in systemic hemodynamics or end-organ perfusion between the two resuscitative approaches他山之石，可以攻玉他山之石，可以攻玉.输注血液成分与凝血功能异常管理输注血液成分与凝血功能异常管理RBC:血浆：血小板血浆：血小板 a target haemoglobin (Hb) of 7 to 9 g/dl (Grade 1C) A restrictive transfusion regimen (Hb transfusion trigger 7.0 g/dl) resulted in
30、fewertransfusions as compared with the liberal transfusion regimen(Hb transfusion trigger 1.5倍）血小板血小板platelets beadministered to maintain a platelet count above 50 109/l (Grade 1C). maintenance of a platelet count above 100 109/l in patients with multiple trauma who are severely bleeding (Grade 2C).
31、 an initial dose of four to eight platelet concentrates or one aphaeresis pack (Grade 2C)a unit of whole blood contains7.5 1010 platelets on average and should increasethe platelet count by 5 to 10 109/l in a 70 kg recipient.Aphaeresis platelet concentrates generally contain approximately 3 to 6 101
32、1 platelets, depending on local collection practice, and physicians should be cognisantof the doses provided locally. A pool of four to eight platelet concentrates or a single-donor aphaeresis unit is usually sufficient to provide haemostasis in a thrombocytopaenic, bleeding patient. 注意点：Coagulation
33、 supportFibrinogen and cryoprecipitate适应症适应症 functional fibrinogen deficit or a plasma fibrinogen level of less than 1.5 to 2.0 g/l (Grade 1C). an initial fibrinogen concentrate dose of 3 to 4 g or 50 mg/kg of cryoprecipitate, which is approximately equivalent to 15 to 20 units in a 70 kg adult. Rep
34、eat doses may be guided by thrombelastometric monitoring and laboratory assessment of fibrinogen levels (Grade 2C).1:1:1 (pRBC/plasma/platelets）靶向目标：组织灌注，血压？靶向目标：组织灌注，血压？产后出血血液制品治疗趋势与效果收缩压收缩压90mmHg90mmHg，PH7.1PH7.1体温体温 34 2.0CINR 2.0，血小板，血小板 50,000/mm 50,000/mm红细胞红细胞新鲜冰冻血浆新鲜冰冻血浆血小板血小板冷沉淀冷沉淀Round 16
35、units6 units6 units10unitsRound 26 units6 units20unitsRound 3活化活化7因子因子注意点：其他药物选择Antifibrinolytic agentsAntifibrinolytic agents be considered in the bleeding trauma patient (Grade 2C). Fibrinolysis in all patients and administration of antifibrinolyticagents in patients with established hyperfibrinol
36、ysis(Grade 1B)氨甲环酸：10 to 15 mg/kg followed by an infusion of 1 to 5 mg/kg per hourrFVIIamajor bleeding in blunt trauma persists despite standard attempts to control bleeding and bestpractice use of blood components (Grade 2C).RBCs, platelets, FFP and cryoprecipitate/fibrinogen resulting in Hct above
37、 24%, platelets above 50,000 109/l and fibrinogen above 1.5 to 2.0 g/l内容五内容五降低严重并发症降低严重并发症血糖血糖循环、血液、呼吸循环、血液、呼吸水、电解质、酸碱水、电解质、酸碱 满足标准；理论基础满足标准；理论基础广州孕产妇救治中心产后出血患者救治 AAirway maintenance，-（气道与通道维持） BBreathing and ventilation，-（呼吸与通气） CCirculation with hemorrhage control-（循环与控制出血） DDrug-（药物） EExposure wi
38、th environmental control & evaluation(环境与评价） FFetus-（胎儿处理）陈敦金，等。中国实用妇科与产科杂志，陈敦金，等。中国实用妇科与产科杂志，2012,6:45-482012,6:45-48Minimise blood loss, restore tissue perfusion and achieve haemodynamic stabilityA and B(呼吸维持）-团队人员组织要求-呼吸通道呼吸通道A-静脉通道-人员组织B-呼吸维持Availability of appropriate emergency supplies in a re
39、suscitation cart (crash cart) or kitDevelopment of a rapid response teamDevelopment of protocols that include clinical triggersUse of standardized communication tools for huddles and briefs (eg, SBAR)Implementation of emergency drills and simulations保证患者：DO2=1.38HbSaO2CO10 CaO2一定时，DO2由心排量(CO)决定 CO则又
40、取决于每搏输出量(SV)和心率(HR)， COSVHR SV取决于心肌收缩力和心室前、后负荷 前、后负荷则又分别与血容量及外周血管阻力有关保证患者组织灌注.升压药物选择：目标：MAP60-65mmHg去甲肾上腺素去甲肾上腺素 from 0.01 to 3.3mg/kg/min多巴胺 less than 5 mg/kg/minute, dopaminergic receptors are activated, 肾、肠系膜血管扩张 5 to 10 mg/kg/minute, b1-adrenergic effects predominate, increasing cardiac contract
41、ility and heart rate above 10 mg/kg/minute, a1-adrenergic effects predominate, leading to arterial vasoconstriction and an increase in blood pressure.肾上腺素根据检测结果判断：乳酸水平与碱缺失（监测）乳酸乳酸 in whom lactate levels returned to the normal range (2 mmol/l) within 24 hours survived. Survival decreased to 77.8% if
42、normalisationoccurred within 48 hours and to 13.6% in those patients in whom lactate levels were elevated above 2 mmol/l for more than 48 hours碱缺失 the extent of base deficit into three categories, mild (-3 to -5 mEq/l), moderate (-6 to -9 mEq/l) and severe (-10 mEq/l), and established a significant
43、correlation between the admission base deficit and transfusion requirements within the first 24 hours and the risk of post-traumatic organ failure or death凝血功能INRPTAPTT改变思路后治疗效果（Obstet Gynecol 2006;107:97783）基本特征基本特征 年龄年龄(y) 36.5 +/-6.0 34.2 (y) 36.5 +/-6.0 34.2 +/-+/- 5.9 .23 5.9 .23 产次产次 1 (03) 1
44、(05) .701 (03) 1 (05) .70 瘢痕子宫瘢痕子宫 6 (50.0) 32 (65.3) .336 (50.0) 32 (65.3) .33结果孕产妇死亡死亡 2 (16.7) 0 (0.0) .0362 (16.7) 0 (0.0) .036* * 酸中毒酸中毒 7.23 (6.87.39) 7.34 (7.087.44) .0047.23 (6.87.39) 7.34 (7.087.44) .004* *低体温（低体温（C) 35.2 (30.235.8) 36.1 (35.237.8) .001C) 35.2 (30.235.8) 36.1 (35.237.8) .00
45、1* *凝血功能障碍凝血功能障碍 7 (58.3) 15 (30.6) .097 (58.3) 15 (30.6) .09子宫切除子宫切除 6 (50.0) 18 (36.7) .516 (50.0) 18 (36.7) .51输血输血(mL) 1,313 (mL) 1,313 +/-+/- 1,029 1,194 1,029 1,194 +/-+/- 1,547 .80 1,547 .80手术持续时间手术持续时间(min) 185 (min) 185 +/-+/- 91 184 91 184 +/-+/- 79 .99 79 .99气管插管气管插管 24 h 7 (58.3) 16 (32.
46、7) .1824 h 7 (58.3) 16 (32.7) .18 Good doctors use both individual clinical expertise and the best available external evidence, and neither alone is enough. Without clinical expertise, practice risks becoming tyrannised by evidence, for even excellent external evidence may be inapplicable to or inappropriatefor an individual patient. Without current best evidence, practice risks becoming rapidly out of date, to the detriment of patients整体思路：需要遵循原则整体思路：需要遵循原则出血之后评估出血之后评估组织灌注情况（组织灌注情况（BP.P.T.CRT.Mentation)-BP.P.T.CRT.Mentation)-我们处理我们处理出血原因出血原因子宫收缩乏力.软产道损伤进一步出血原因胎盘问题.凝血功能快速止血！快速止血！
