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1、,Transfusion Alternative&Fluid Restriction,許廣南E-mail：terence.hsufresenius-,The Latest Artificial ColloidFluid Replacement - Products Crystalloids overload vs Fluid Restriction postoperative morbidity Combine Colloid：Improve Outcome 大量証據支持HES能有效改善微循環灌注及減少微血管滲漏 Allergic Reactions with Colloid Solution
2、s Take Home Message Contra-Indication,The Latest Artificial Colloid“Voluven”,An Ideal Fluid,Good Volume EffectVolume Effect 100%Optimal long volume effectKeep vital sign stableExcellent Safety ProfileMinimize the coagulation disturbanceTotal eliminate from Kidney without plasma accumulation No tissu
3、e accumulation,National Research Council USA,1963,Voluven：Good volume Effect,Study results Volume effect 100% Plateau effect 4 hours Volume effect up to 6 hours,Volume effect of 6% HES 130/ 0.4,(Waitzinger et al., 1998),Voluven：良好的安全性凝血功能,Voluven 降低分子量及取代率，使其對凝血功能影響最小，類似Crystalloid,Voluven：良好的安全性腎功能
4、,Voluven對腎功能影響小，即使中、重度腎功能損傷患者仍可安全使用,Voluven：良好的安全性,Voluven的安全性在長期大劑量使用的研究，和嬰幼兒的應用中得到驗証,Voluven：An Ideal Choice for Volume Therapy,Good Volume Effect：100 Volume effect，有效擴充血漿容量時間可達4-6小時。保持血液動力學穩定和微循環灌注良好高度的安全性對凝血功能影響最小對腎功能影響最小完全經腎臟排出，無血漿蓄積，連續使用或大劑量安全性好殆無组織蓄積,1980New Generation HES,1915World War,1945W
5、orld War,1960War In Vietnam,2000A Class of Its Own,Voluven： A Class of Its Own,Fluid Replacement - Products,請問：欲維持微循環灌注良好，需注意那些*輸液的處理方針?A、VOLUME EFFECT is essentialB、Reduce TISSUE EDEMAC、Reduce CAPILLARY LEAKD、All of ABOVE,* TSCCM 4/2107認證訓練課程,Volume Therapy,Fluid Therapy,NUTRITION,Natural Colloid,A
6、rtificial Colloid,1. Replace acute loss (hemorrhage, GI loss)2. Volume expansion,1. Replace normal loss (IWL + urine+ faecal)2. Nutrition support,Electrolytes,INFUSION THERAPY,Crystalloid,Volume Replacement - Drugs,Steinfath 2003,Isotonic crystalloid solutions with physiologic electrolyte compositio
7、n,Limiting factors:- Large amounts necessary (300-400 ml substitutes for 100 ml plasma)- Fast distribution from intravascular space into interstice (oedema!)- Reduction of colloid-osmotic pressure resulting in extravasation - Fast renal elimination - Larger volume deficiencies should be treated with
8、 a combination of crystalloids and colloids,Crystalloids for Volume Replacement“,A balanced approach to fluid management is recommended.blood loss may be replaced with colloid on a volume to volume basis,Crystalloid will induce tissue edema,Drawbacks of over used Crystalloid,正常肺组織，肺泡内空腔（ ）,Crystallo
9、id will induce tissue edema,肺组織水腫，肺泡腔内充满粉染的水腫液（）,From H.J. Buhr, DEPT. OF Surgery, CHARIT-UNIVERSITY BERLIN,正常胃腸粘膜組織,輸注大量乳酸林格液後,組織水腫,Crystalloid will induce tissue edema,Frankel HL, et al. J Trauma.1996;40(2):231-240,Volume replacement and microcirculation,RBC,RBC,Edema interstitial,“Shock”,“Non-sho
10、ck”,Normal interstitial,No flow,RBC,RBC,flow,endothelium,術後併發症與那些因素關係最為密切？（請選擇）,患者一般情況(如年齡、ASA評分）；手術時間和出血量；血液動力學指標（如：心率、血壓、血氧飽合度）；微循環和臟器灌注；,一般普遍觀點,術後併發症和那些因素關係最為密切？1. 患者一般情况（如：年齡、ASA評分） 20.6%2. 手術時間和出血量 28.8%3. 血液動力學指標（如：心率、血壓、血氧飽合度） 40.6%4. 微循環和臟器灌注 10.0%,外科術後併發症究竟和什麼相關？,Bennett-Guerrero E. et al.
11、Anesth Analg.1999;89:514-519,一項針對術後延遲出院原因的前瞻性研究,Study Design（n=438）,骨外科：如髋關節成型術,一般外科：超過2小時以上的剖腹手術，如肝部分切除術、胰腺、胃腸腫瘤手術,泌尿外科：根治性前列腺切除術、根治性膀胱切除術、根治性腎切除術,血管外科：腹主動脈瘤修補術,婦科：經腹子宫切除術,Bennett-Guerrero E. et al. Anesth Analg.1999;89:514-519,結果：術後併發症的機會27%,結論對術後併發症有預測意義的指標,ASA評分 手術創傷的指標（如：手術時間、出血量）血流動力學指標（如：心率、血
12、壓、血氧飽和度）與術後併發症間有一定相關性微循環和组織灌注的指標（如：動脈血鹼剩餘、胃粘膜PHi）Crystalloid量和術後併發症密切相關,Bennett-Guerrero E. et al. Anesth Analg.1999;89:514-519,Volume Replacement - Drugs,Colloids,Natural colloids,GelatinDextran Starch,Artificialcolloids,Albumin,Plasma,Guideline for the use of Fresh-Frozen PlasmaReplacement of sing
13、le factor deficienciesImmediate reversal of warfarin effectVitamin K deficiency associated with active bleedingAcute DICThrombotic thrombocytopenic purpuraInherited deficncies of inhibitors of coagulationConditional uses:Massive transfusionLiver diseasesCardiopulmonary bypass surgery,October 1998, V
14、ol. 88, No. 10 SAMJ,Plasma,838 critically ill patients - euvolaemic.Blood transfusion trigger1. Hb 70 g/L (obtained Hb-range 70-90 g/L)2. Hb 100 g/L (obtained Hb-range 100-120 g/L)Overall 30 day 1 - 18.7% mortality2 - 23.3%APACHE 20 1 - 8.7%2 - 16.1%55 years of age1 - 5.7%2 - 13.0%Patients with sign
15、if.1 - 20.5%cardiac disease2 - 22.9%,Hbert et al. N Engl J Med 1999; 340: 409-417,P-RBC,Plasma,Tetrastarch,Pentastarch Gelatins,FFP(albumin),130K 200K 3035K 69K 69K,25%,Albumin,6% 10% 35% 25% 5%,68 hrs 812 hrs 1 hrs 6 hrs,降低 降低 無助 降低 無助,36 60-80 20 120 25,快速穩定 快速穩定 不足 價格昂貴 稍可,可防止 可防止 無助 critical時亦滲漏
16、 critical時亦滲漏,無 無 Prion? AIDS/Hepatitis AIDS/Hepatitis,平均分子量 劑型 Volume effect (T1/2) 組織水腫 Oncotic Pressure (mmHg) 提昇血壓 微血管滲漏 感染,All Colloid Are Not The Same,Prospective、Randomized studyElective cardiac surgery（n=60）Fluid regimen： A：Routine Crystalloid B：Routine Crystalloid6%HES觀察指標： Cardiac output通過
17、經食道多普勒超音波系统反應 胃粘膜灌注通過胃粘膜内PH值反應,Combine Colloid是改善手術預後的有效方法,Mythen MG. et al. Arch Surg.1995;130:423-429,Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery,Combine Colloid：Improve Outcome,10,20,0,30,40,50,60,%,腸粘膜灌注不足發生率,P0.001,1,2,0,3,4,5,
18、6,發生大併發症的病例數,P=0.01,2,4,0,6,8,10,12,天,Hospital Stay (Day),P=0.011,0.4,0.8,0,1.2,1.6,2.0,2.4,天,ICU Stay (Day),P=0.023,Mythen MG. et al. Arch Surg.1995;130:423-429,Colloid是改善微循環的有效方法,Elective Abd. Surgery（n=42）,HES 130/0.4 (n=21),Ringers液 (n=21),比較組織氧分壓,隨機,Volume Therapy to Keep CVP at 8-12mmHg,Lang e
19、t al. Anesth Analg 2001;93:405-409,Colloids Versus Crystalloids and Tissue Oxygen Tension in Patients Undergoing Major Abdominal Surgery,平均液體輸注量,術後次日组織氧分壓改變,%,+59%,-23%,Colloid：改善组織氧分壓,Lang et al. Anesth Analg 2001;93:405-409,0,3000,6000,9000,12000,ml,0,20,40,60,-20,-40,HES 130/0.4（Voluven）,Inclusio
20、n Criteria：Elective GS、OBS、PS or Uro surgery (Estimate blood loss 500ml）,Elective non-cardiac Surgery patients（n=90）,Crystalloid (HES-NS 6%)(n=30),Electrolyte Balanced HES (HES-BS 6%)(n=30),Ringers 液 (RL)(n=30),隨機,比較各組術後併發症出現情況,Combine Colloid是改善手術預後的有效方法,Moretti EW et al. Anesth Analg 2003,96:611-6
21、17,Intraoperative Colloid Administration Reduces Postoperative Nausea and Vomiting and Improves Postoperative Outcomes Compared with Crystalloid Administration,Moretti EW et al. Anesth Analg 2003,96:611-617,Combine Colloid：Improve Outcome,Discussion：Elective non-cardiac surgery resuscitation with Co
22、lloid reduce complications,Conclusion,穩定的血流動力學是保証微循環灌注的前提；單獨補充Crystalloid不能有效改善血流動力學指標和微血管循環灌注障礙；Colloid能有效改善血流動力學指標和微循環灌注障礙；改善血流動力學指標、微循環灌注障礙的理想選擇：,Crystalloid + Colloid,Hospital Market Colloids - Germany 1984 - 2004,Hydroxyethyl Starch(HES)中分子羥乙基澱粉,Voluven 6%,微血管滲漏症,CLS (Capillary Leak Syndrome)病理
23、生理機轉 炎症介質大量釋放，引起微血管内皮细胞損傷，血管通透性增加，造成間質水腫、组織缺氧，繼而加重微血管内皮细胞損傷，形成惡性循環，引起器官功能障礙。病因 Severe Trauma、Major surgery、Critical Infection等，如急性重症胰腺炎、絞窄性腸阻塞、急性彌漫性腹膜炎 。主要表現補充大量液體難以纠正休克，全身水腫；多器官功能衰竭，ARDS等。,組織细胞,組織間隙,微血管,细胞内液,组織間液,血漿,5%,15%,40%,血管活性和炎性介質大量釋放微血管通透性增加白蛋白漏出,水流出增加加重组織水腫,組織損傷導致微血管滲漏的過程模式,From H.J. Buhr,
24、DEPT. OF Surgery, CHARIT-UNIVERSITY BERLIN,顯微鏡下的微血管滲漏,Mc Donald et al., Microcirculation,1999,微血管滲漏 - 活體顯微鏡檢查,活體顯微鏡觀察到的微血管滲漏,Systemic Inflammatory Response Syndrome (SIRS),from Dieterich, Tbingen,HES - Adhesion Molecules,Hofbauer et al.; Transfusion 1999,HES - Capillary Leak,Gosling et al.; Trauma C
25、are 1999,Properties of Resuscitation fluids,Crystalloid Gelatine Albumin Voluven,0 30 000 Da 68 000 Da 70-150 000 Da,In vivo MW,Concentration0%,Concentration3.5%,Concentration5 %,Concentration6 %,大量証據支持HES能有效改善微循環灌注及減少微血管滲漏,Boldt J. et al. Shock. 2006;25(2):103-116,Allergic Reactions with Colloid So
26、lutions,Laxenaire et al., Ann Fr Anes Ranim 1994,HES why low Rate of Allergic Reactions?,Dieterich et al., Anesth Analg 1998,Glycogen Amylopectin (Starch)14 16 %Branching 5 6 % Branching site,N Engl J Med 2004;350:2247-56,6997位住加護病房病人分成3497位接受4%白蛋白, 3500 位接受N/S, 28天後再觀察兩組病人的死亡率.,28天後,兩組的死亡人數分別是726 (
27、白蛋白組)和729 (N/S組),器官衰竭的比例一樣,住ICU和住院天數沒有分別,機械性通氣,腎臟替代治療的天數也沒有分別,重症病人在使用4%白蛋白跟N/S, 28天的臨床結果是一樣的,Probability of survival,在所有重症病人中,臨床結果皆沒有差異,但發現在頭部外傷的病人,使用4% albumin可能會增加死亡率,N Engl J Med 2004;350:2247-56,SAFE,Standard protocol： 1、CPP60mmHg2、Colloid 10% HES 1000ml/day combine with crystalloid3、Manage ICP、
28、renal function.,10% HES can be used no definite bleeding complication*Balanced fluid management can achieved without causing serious pulmonary complications,Effect of fluid loading with saline or colloids on pulmonary permeability, edema and lung injury score after cardiac and major vascular surgery
29、,Study design:,Br J Anaesth 2006;96:21-30,Single center, prospective, single-blinded clinical.67 mechanically ventilated patients were randomly assigned to receive saline, gelatin 4%, HES 6% or albumin 5% 90 min fluid loading with target central venous pressure of 13mmHg and PCWP of 15mmHg, within 3
30、h after cerdiac or major vascular surgery.Record haemodynamics and ventilatory variables and took chest rediographs.,Effect of fluid loading with saline or colloids on pulmonary permeability, edema and lung injury score after cardiac and major vascular surgery,Result:,Br J Anaesth 2006;96:21-30,、Mor
31、e saline was infused than colloid solution (P0.005)、COP increased in the colloid groups and decreased in patients receiving saline.、Cardiac output increased more in the colloid group.、HES may ameliorate increased permeability.,Crystalloid vs. ColloidEarly 1990s,“The end of the crystalloid era”,Inter
32、stitial edema (brain, lung, G-I, etc),Fluid failure,Twigley & Hillman, Anaesthesia, 1985,A fluid withont volume effect,will strangulate the vessel.,Interstitial edemaTissue hypoperfusion,If some is good,More is better ?,Early is better,Functional hemodynamic protocol,Pinsky & Vincent. Crit Care Med
33、33:1119-22, 2005,SvO2,Resuscitation endpoint: MBP 65 mmHg,血壓,血流,血氧,血色,Take Home Message,多重創傷死亡的因素大都為：不可逆的休克；呼吸機能不全且嚴重組織缺氧應重視使用Colloid： CrystalloidColloid (Voluven) 能更好改善微循環 Voluven是避免微血管滲漏症的理想選擇Voluven（Tetra starch130/0.4）：The latest HES (Effective and Safety)Recommend dosage：Crystalloid for dehydra
34、tion Initial with isotonic crystalloid first：20ml/kg Then Colloid volume to volume substitute by blood lossVoluven up to 3,500ml,Trauma Fluid Regimen,Based on 70kg b.w.* Dehydration: Start crystalloid first or continuously.,Volume Therapy (For expansion),Then Colloid (Voluven) up to 3,500ml,Fluid Th
35、erapy (For dehydration),*Initial with isotonic crystalloid 20ml/kg,Take Home Message,限制術中輸液量可有效減少術後併發症及死亡率(Annual of surgery 2003;238:641-648)限制輸液不會造成術中或術後的低血壓並可減少住院天數、降低併發症(Anesthesiology. 2005;103(1):25-32)適當的輸血是必須的；Hb值7-9是較佳的時機；心臟疾病及65y/o以上老年人Hb值10是較佳的(N Engl J Med 1999; 340: 409-417)應重視使用Colloid
36、維持血液動力學穩定並避免術後水腫及微血管滲漏： CrystalloidColloid (Voluven) 能更好改善微循環、減少輸液量 Voluven是避免微血管滲漏症的理想選擇Recommend dosage：( Anesth Analg 2005;101:601-5)Crystalloid first for dehydration Keep urine output 0.5ml/kg/hr, some paper recommend 0.3ml/kg/hr Colloid volume to volume substitute by blood lossVoluven up to 3,5
37、00ml (50ml/kg/day)Blood component therapy only for oxygenation and clotting factor,Recommend Dosage:,Take Home Message,微循環障礙在術後普遍存在；與術後併發症密切相關；術後應重使用Colloid： CrystalloidColloid (HES) 能更好改善微循環 HES是避免微血管滲漏症的理想選擇Voluven（Tetra starch130/0.4）：The latest HES (Effective and Safety)Recommend dosage： Major E
38、lective SurgeryHES 500ml X 3天 Major Trauma Surgery HES 500-1000ml X 3天,Post OP Fluid Regimen,From H.J. Buhr, DEPT. OF Surgery, CHARIT-UNIVERSITY BERLIN,請問：Voluven 6% 比起HAES-Steril更適合用於何種病患族群？A、RENAL IMPAIRED PATIENTSB、ICU CAPILLARY LEAKAGE SYNDROME C、PERFUSION RECOVERYD、COAGULAPATHY Pt,Voluven：Safet
39、y and Economics,*Blood saving = Cost saving = Infection reduction = Mortality reduction,Contra-Indication,Severe hypernatremia or severe hyperchloremiaFluid overloadRenal failure with oliguria or anuriaIntracranial bleedingHypersensitivity to hydroxyethyl starches,Thanks for your attention！,Transfusion Alternative&Fluid Restriction,
