賀斯和萬汶用于急性高容量血液稀釋對術(shù)前高凝患者凝血功能的影響

1、賀斯和萬汶用于急性高容量血液稀釋對術(shù)前高凝患者凝血功能的影響張大志 李世忠 張曉光 楊慶國 孫曉雄Effects of acute hypervolemic hemodilution induced by HAES-steri or voluven on coagulation function in preoperative hypercoagulable patientsZhangDazhi, LiShizhong, ZhangXiaoguang, YangQingguo, Sun Xiaoxiong (Department of anesthesiology, Beijing Ji Sh

2、uitan hospital, Beijing 100035, China)【Abstract】 Objective To evaluate the effects of acute hypervolemic hemodilution(AHH) induced by HAES-steri(6%HES 200/0.5) or voluven（6%HES 130/0.4）on coagulation function in preoperative hypercoagulable patients. Methods Thirty adult patients with hypercoagulabi

3、lity state, undergoing coxa or lower limbs fracture surgery, were randomly divided into two groups: HAES-steri group (H group) and voluven group (V group). Each group had 15 patients. They respectively received intravenous infusion of 15ml/kg HAES-steri (H group) or voluven(V group) within 30 minute

4、s before operation. The venous blood samples were taken before and 30 minutes after the infusion, to determine haemoglobin (Hb), haematocrit (Hct), platelet count (PLC), prothrombin time (PT), activated partial thromboplastin time(APTT), D-dimer(D-D) and fibrinogen(FIB).The following two conditions

5、together are considered as preoperative hypercoagulability state. First, the patients suffered from fracture of coxa or lower limbs for more than 6 days. Second, the following laboratory results are obtained more than two items: D-D500ug/L;FIB4g/L, PLC300109/L, PT and APTT shorten. Results The decre

6、ases in Hb and Hct were statistically significant in both groups(P 0.05). PT was significantly prolonged after hemodilution in both groups, but there was no significant change in APTT as well as D-D(P 0.01). FIB reduced significantly only in H group(P0.01). Hb was greater in V group compared with H

7、group after hemodilution(P 0.05). Conclusion AHH induced by HAES-steri or voluven did not enhanced coagulation function in preoperative hypercoagulable patients. Voluven and HAES-steri compromised blood coagulation to the same degree, but slightly improve the hypercoagulability.【Key words】Hetastarch

8、；Hemodilution；hypercoagulability state；hemopexis作者單位：100035 北京市，北京積水潭醫(yī)院麻醉科 賀斯和萬汶用于急性高容量血液稀釋對術(shù)前高凝患者凝血功能的影響北京積水潭醫(yī)院麻醉科 100035張大志 李世忠 張曉光 楊慶國 孫曉雄【摘要】 目的 觀察兩組術(shù)前存在高凝狀態(tài)患者分別用賀斯(6%HES 200/0.5)和萬汶（6%HES 130/0.4）行急性高容量血液稀釋(AHH)對凝血功能的影響。 方法 擇期行髖部或下肢骨折手術(shù)高凝患者30例，ASA 級，隨機分為賀斯組和萬汶組，每組15例。入手術(shù)室后30分鐘內(nèi)輸入賀斯或萬汶15ml/kg。于輸

9、液前及輸液后30min時采靜脈血測定血紅蛋白(Hb)、紅細胞比容(Hct)、血小板計數(shù)(PLC)、凝血酶原時間(PT)、部分凝血活酶時間(APTT)、D-二聚體(D-D)、纖維蛋白原(FIB)含量。術(shù)前高凝患者入選標準為：髖部或下肢骨折病人手術(shù)，臥床時間不小于6天并且化驗室檢查達到以下兩項或兩項以上：D-D不小于500ugL-1 ,纖維蛋白原不小于4gL-1 ,PT、APTT小于正常參考值低限，血小板計數(shù)不小于300109L-1。具備下述條件之一者排除本研究之外：術(shù)前血紅蛋白低于110gL-1；術(shù)前Hct小于30%；嚴重心、肝、腎功能損害；有高血壓病史；內(nèi)分泌功能異常；對羥乙基淀粉過敏者。 結(jié)

10、果 與輸液前比較，兩組患者輸液后30min時Hb及Hct均顯著降低(P 0.05）。兩組輸液后30minPT均顯著延長(P 0.01), APTT和D-D無顯著變化, FIB僅在賀斯組顯著減少(P0. 01)。萬汶組輸液后30min時Hb較賀斯組高(P 0.05)。 結(jié)論 賀斯和萬汶用于AHH并不增強高凝患者的凝血功能。萬汶和賀斯對術(shù)前高凝患者凝血功能的影響雖無顯著統(tǒng)計學差異，但有一定改善術(shù)前高凝狀態(tài)的作用?！娟P(guān)鍵詞】 羥乙基淀粉；血液稀釋；高凝狀態(tài)；血液凝固 急性高容量血液稀釋(AHH)作為一種血液保護的方法已經(jīng)廣泛應(yīng)用于臨床。血液稀釋可降低血液粘滯性、維持組織氧供需平衡,但用不同的液體血液

11、稀釋可能會對機體的凝血功能產(chǎn)生不同影響。絕大多數(shù)研究發(fā)現(xiàn)晶體液血液稀釋可促進凝血功能造成高凝狀態(tài)1 Ng KFJ, Lam CCK, Chan LC. In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial. Br J Anaesth, 2002, 88: 475 - 480. 2 王庚, 吳新民. 急性等容性血液稀釋與凝血狀態(tài). 中華麻醉學雜志,2001,21:645-648.3 區(qū)錦燕, 廖榮宗, 周曙等. 股骨多段閉合骨折病人術(shù)前凝血功能的變化. 中華麻醉學雜志,

12、2004, 24:534-536.4 董小黎. D-二聚體及其抗體在心血管疾病中的應(yīng)用. 首都醫(yī)科大學學報, 2000, 1:21. ，而多數(shù)認為羥乙基淀粉可損害凝血功能，但血液稀釋時可使機體處于高凝狀態(tài)5 Entholzner, EK, Mielke, LL, Calatzis, AN, et at. Coagulation effects of a recently developed hydroxyethyl starch (HES 130/0.4) compared to hydroxyethyl starches with higher molecular weight. Acta

13、Anaesthesiologica Scandinavica. 2000,44: 1116-1121.6 Jamnicki, M, Zollinger, A , Seifert B, et al. Compromised blood coagulation: an in vitro comparison of hydroxyethyl starch 130/0.4 and hydroxyethyl starch 200/0.5 using thrombelastography. Anesthesia & Analgesia, 1998, 87: 989-9937 vonRoten, IC, M

14、adjdpou, C, Frascarolo, P. et al. Molar substitution and C2/C6 ratio of hydroxyethyl starch: influence on blood coagulation. Br J Anaesth, 2006, 96: 455-463. 8 Stump DC, Strauss RG, Henriksen RA.et al. Effects of hydroxyethyl starch on blood coagulation,particularly factor VIII. Transfusion 1985: 25

15、: 349354. 。本試驗意圖通過觀察術(shù)前處于高凝狀態(tài)骨折病人AHH后各項凝血參數(shù)的變化, 探討用賀斯和萬汶行AHH對術(shù)前高凝患者凝血功能的影響。資料和方法病例選擇及分組選取擇期行髖部或下肢骨折手術(shù)術(shù)前存在高凝患者30例, ASA III。男28例、女2例，年齡1854歲。隨機分為2組,賀斯(H組)和萬汶組(V組)，每組15例。術(shù)前高凝患者入選標準為：髖部或下肢骨折病人手術(shù)，臥床時間不小于6天并且化驗室檢查達到以下兩項或兩項以上：D-D不小于500ugL-1 ,纖維蛋白原不小于4gL-1 ,PT、APTT小于正常參考值低限，血小板計數(shù)不小于300109L-1。具備下述條件之一者排除本研究之外

16、：術(shù)前血紅蛋白低于110gL-1；術(shù)前Hct小于30%；嚴重心、肝、腎功能損害；有高血壓病史；內(nèi)分泌功能異常；對羥乙基淀粉過敏者。 血液稀釋方法及觀察指標 入手術(shù)室后開放外周靜脈，每組病人術(shù)前30分鐘內(nèi)輸入15 mlkg-1賀斯或萬汶（均為費森尤斯卡比醫(yī)藥有限公司生產(chǎn)，德國）。分別于血液稀釋前、稀釋后30min時采集靜脈血測定血紅蛋白(hemoglobin，Hb)、紅細胞比容(haematocrit，Hct)、血小板計數(shù)(platelet count，PLC),凝血酶原時間(prothrombin time，PT)、部分凝血活酶時間(activated partial thromboplast

17、in time，APTT)、D-二聚體(D-dimer，D-D)和纖維蛋白原(fibrinogen，F(xiàn)IB)。同時監(jiān)測病人心率(HR)、收縮壓(SBP)、舒張壓(DBP)、平均動脈壓(MAP)、脈氧飽和度(SpO2)和心電圖(ECG)。 統(tǒng)計學處理 采用SPSS11.5統(tǒng)計軟件進行統(tǒng)計分析，計量資料用均數(shù)標準差（ s）表示，組內(nèi)比較采用配對t檢驗，組間比較采用團體t檢驗。P0.05）。輸注賀斯和萬汶過程中HR、SBP、DBP、MAP、SpO2、ECG平穩(wěn),無心律失常出現(xiàn)。血液稀釋后Hb及Hct在兩組均顯著降低(P 0.05）。稀釋后Hb賀斯組比較萬汶組低(P0.05)。見表1。表1.兩組稀釋前

18、后血常規(guī)檢查結(jié)果的變化（ s）指標 組別 稀釋前 稀釋后Hb(gL-1) H 122.0016.58 85.4131.08* V 135.2819.94 109.0719.67*Hct H 35.855.58 27.804.52* V 39.115.15 31.315.02*PLC(109L-1) H 334.44105.60 288.0073.00 V 301.85119.38 255.35109.28與稀釋前比較 * P0.01 與賀斯組比較 P0.05 血液稀釋后PT在兩組均顯著延長, APTT和D-D無顯著變化, FIB僅在H組顯著減少(P0.01)。組間各凝血指標均無顯著性差異。見表

19、2。表2. 兩組稀釋前后實驗室凝血指標的變化（ s）指標 組別 稀釋前 稀釋后PT(s) H 11.830.48 12.830 .50* V 11.700.71 12.861.09APTT(s) H 24.563.30 27.312.90 V 25.764.64 29.705.51 FIB(gL-1) H 501.5561.81 401.4269.51 V 483.38108.03 405.05122.81D-D(ugL-1) H 713.00422.34 557.22279.87 V 531.02215.03 475.12204.81 與稀釋前比較 * P500ugL-1作為陽性標準。 兩組病人在輸液中HR、MAP、SpO2