止血芳酸对体外循环心脏手术中血小板膜糖蛋白受体GP1b的保护作用

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体外循环中止血芳酸对血小板的保护作用

目的：探讨止血芳酸在体外循环中对血小板的保护作用及其临床意义。方法：测定止血芳酸组和对照组血小板数量、出血量和输血量,及体外循环前后血浆α－颗粒膜蛋白（ＧＭＰ－１４０）,血栓烷Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１a(6-k-PGF1a）的浓度变化。结果,体外循环术后血小板计数组明显高于对照组,出血量明显少于对照组。ＧＭＰ－１４０、ＴＸＢ２上升幅度小于对照组,二者相比差异显著（Ｐ＜０．０５）。结论：止血芳酸在体外循环术中可以起到保护血小板,减少术后出血的作用。     

抑肽酶和止血芳酸在心肺转流中抗纤溶和止血作用的研究

目的 比较抑肽酶和止血芳酸在心肺转流(CPB)中抗纤溶作用及对术后止血量的影响。方法 41例首次择期心脏瓣膜替换术成年患者,随机双盲分为抑肽酶组(A组)20例和试验组(P组)21例。于诱导后、给试验药后5min、CPB 30 min、鱼精蛋白中和10 min和手术后2h,采血测定血浆纤溶酶(Plm)活性,血浆纤维蛋白(原)降解产物(FDP)和卜-二聚体(D-Dimers)浓度,并观察术后48h胸腔及心包引流量。结果 给试验药后5min所有检测指标均无明显变化。Plm在CPB 30min达最高值(P<0.01),中和后10min有所降低,但仍高于基础值(P<0.01),术后2h A组降至基础值水平,P组仍高于基础值(P<0.05),两组相比中和后10 min P组Plm活性明显高于A组(P<0.01),其余各时点均无显著差异。FDP和D-Dimers于CPB 30 min显著增高(P<0.01),中和后10min达到最高值,术后2h A组FDP、D-Dimers和P组的FDP均降至基础值水平,P组D-Dimers仍明显高于基础值(P<0.01)。两组相比CPB 30 min A组D-Dimers含量显著高于P组。两组术后48h内胸液引流量相比无统计学差异。结论 预防性应用抑肽酶或止血芳酸(20mg/kg)可部分抑制CPB中的纤溶亢进;二者的抗纤溶和减少首次手术出血量的作用相近。     

止血环酸在心肺转流术中对凝血功能的影响

目的 应用sonoclot分析仪(SCT)观察止血环酸在心脏手术中的血液保护效果。方法36例心脏手术患者分成工组(抑肽酶,n=12)、Ⅱ组(止血环酸,n=12)和Ⅲ组(非用药组,n=12)。Ⅰ、Ⅱ组在心肺转流(CPB)下完成心脏手术,Ⅲ组则为非CPB下的冠脉搭桥手术。应用SCT观察切皮前和鱼精蛋白中和肝素后的凝血和血小板(Plt)功能的变化。结果 sonACT在T_1时点Ⅲ组为(123.21±18.58)s,明显高于Ⅰ组的(110.36±24.72)s和Ⅱ组的(106.09±13.91)s(P均<0.05);纤维蛋白凝集率(clot rate)、Plt功能在T_1与T_2时点三组之间均无显著差异。Plt在T_2时点Ⅲ组则明显高于Ⅰ、Ⅱ组。Ⅰ、Ⅱ组在T_2时点的Plt较T_1下降非常显著(P<0.01),Ⅲ组则无明显改变。结论 止血环酸对CPB下心脏手术患者凝血与Plt功能的影响与抑肽酶相似,非CPB下冠状动脉搭桥术对血液系统的影响明显减轻。     

止血芳酸对体外循环心脏手术中血小板功能的保护作用

目的：研究止血芳酸（ＰＡＭＢＡ）对体外循环心肺转流（ＣＰＢ）心脏手术中血小板功能的保护作用。方法：２２例择期心脏瓣膜置换术患者，随分为两组，观察组于麻醉后切片前经中心静脉给予给予ＰＡＭＢＡ ２０ｍｇ／ｋｇ（其中的４００ｍｇ预充体外循环机内），对照组不给药。在ＣＰＢ前、ＣＰＢ后３０分钟、ＣＰＢ结束、鱼精蛋白中和肝素后２０分钟四个时点检测血小板计数、血小板聚集功能和血小板膜糖蛋白ＧＰＩｂ和ＧＰⅡｂ／Ⅲ     

止血环酸对体外循环中血小板的保护作用

止血环酸对体外循环中血小板的保护作用马松峰乔峻张立生作者单位：８３００５３新疆医学院第一附属医院心外科体外循环术后渗血原因复杂，其中血小板功能损伤及数量减少是重要原因之一。因此血小板的保护一直受到临床研究的关注〔１〕。本研究旨在探讨止血环酸抑制纤溶酶...     

抑肽酶和止血芳酸在体外循环中的应用

目的：观察应用抑肽酶和止血芳酸对体外循环后血小板及出血量的影响。方法：328例体外循环分为对照组和实验组，观察术前、术后的血小板数，术中、术后用血量及术后引流量。结果：体外循环后血小板减少，但两组无明显差异（P＞0．05），实验组引流量、用血量明显减少（P＜0．05）。结论：抑肽酶和止血芳酸对减少体外循环后渗血有明显效果。     

体外循环中纤溶系统的改变及止血芳酸对其的影响

体外循环中纤溶系统的改变及止血芳酸对其的影响陈良万，薛松体外循环可导致纤溶亢进，从而引起术后非外科性出血和灌注肺等并发症。组织纤溶酶原激活物（ｔ－ＰＡ）和其抑制物（ＰＡＩ）是近年来发现的纤溶系统最关键性物质。本实验通过观察体外循环中ｔ－ｐＡ、ＰＡＩ的...     

体外循环心瓣膜置换术中止血环酸的应用

目的　体外循环心瓣膜置换术中应用止血环酸（ｔｒａｎｅｘａｍ ｉｃ ａｃｉｄ）,观察其对血小板的保护作用。　方法５０ 例心瓣膜置换术的患者随机分为止血环酸组和对照组,用双盲法进行实验。止血环酸组术前静脉注射止血环酸１０ｍ ｇ／ｋｇ,预充液中加５ｍ ｇ／ｋｇ（总量累计超过１ｇ 者,按１ｇ 计算,２／３ ｇ 静脉注射,１／３ ｇ 加入预充液中）;对照组分别加等量生理盐水。测定两组转流前、后血小板粘附率、血小板聚集率、血小板计数,观察术后 ２４ 小时出血量和输血量。结果　转流后两组血小板功能均有下降,但对照组明显低于止血环酸组（ Ｐ＜ ００５）;转流后止血环酸组血小板计数无明显变化（ Ｐ＞ ００５）;转流后对照组血小板计数明显低于转流前（ Ｐ＜ ００１）,且明显低于止血环酸组（ Ｐ＜ ００５）;出血量和输血量止血环酸组均低于对照组（ Ｐ＜ ００５）。　结论　止血环酸能有效保护血小板,明显减少术后出血及输血量。     

Effects of prostaglandin E1 infusion during cardiopulmonary bypass

Effects of continuous prostaglandin E1 (PGE1) infusion 0.03 micrograms.kg-1.min-1 on hemodynamics, body temperature and urine output during cardiopulmonary bypass (CPB) were studied. Systemic vascular resistance was kept significantly lower in PGE1 administration group than control group. Differences between core and peripheral temperature decreased faster in the PGE1 administration group than the control group. Mean arterial pressure was stable at 40mmHg during CPB in the PGE1 group and 60mmHg in the control group. However, there were no significant differences in urine output between the PGE1 administration group (10.8ml.kg-1.h-1) and the control group (9.4ml.kg-1.h-1). This study indicates that continuous PGE1 infusion (0.03 micrograms.kg-1.min-1) is a method of choice for vasodilation and improvement of peripheral perfusion during hypothermia of CPB.     

Effects and arterial concentration of prostaglandin E1 during cardiopulmonary bypass

The effects an infusion prostaglandin E1 (PGE1) on both haemodynamics and PGE1 arterial blood concentration during and after cardiopulmonary bypass (CPB) were studied in 15 patients (eight patients received PGE1 30 ng kg-1 min-1; seven served as controls and did not receive PGE1 administration). Mean arterial blood pressure and systemic vascular resistance were significantly lower in the PGE1 group than in the control group during CPB. There were no statistically significant differences between the two groups with regard to mean pulmonary-artery pressure, central venous pressure, and cardiac or perfusion index. The arterial blood concentration of PGE1 in the control group during CPB was about 50 pg ml-1. In the PGE1 group it increased rapidly after the beginning of CPB and reached a level of 1500 pg ml-1 at 60 min of CPB. After weaning off CPB, PGE1 concentration decreased rapidly to 70 pg ml-1 in spite of the continuous PGE1 infusion. It is concluded that the metabolism of PGE1 is strongly inhibited during CPB and the effects of PGE1 may be unexpectedly heightened. Therefore, the infusion rate of PGE1 during CPB should be 30 ng kg-1 min-1 or less in order to avoid severe hypotension.     

七氟醚预处理联合后处理对大鼠心肌缺血再灌注时血栓素A2和前列腺素I2的影响

Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.     

七氟醚预处理联合后处理对大鼠心肌缺血再灌注时血栓素A2和前列腺素I2的影响

Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.     

七氟醚预处理联合后处理对大鼠心肌缺血再灌注时血栓素A2和前列腺素I2的影响

目的 评价七氟醚预处理联合后处理对大鼠心肌缺血再灌注时血栓素A2和前列腺素I2的影响.方法 健康雄性Wistar大鼠50只,体重250～280 g,采用随机数字表法,将大鼠随机分为5组(n=10):假手术组(S组)、缺血再灌注组(I/R组)、七氟醚预处理组(Spr组)、七氟醚后处理组(Spo组)和七氟醚预处理联合七氟醚后处理组(Spr+po组).I/R组、Spr组、Spo组和Spr+po组采用结扎左冠状动脉前降支30 min时进行再灌注的方法制备心肌缺血再灌注模型,S组仅在左冠状动脉前降支下穿线.Spr组进行七氟醚预处理:于缺血前30 min吸入2.5%七氟醚15 min,洗脱15 min;Spo组进行七氟醚后处理:再灌注前1 min开始吸入2.5%七氟醚,持续5 min;Spr+po组进行七氟醚预处理和后处理.再灌注2 h时取动脉血样,测定血MB型磷酸肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)、血栓素B2(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)的水平和血小板最大聚集率,并计算TXB2与6-keto-PGF1α的比值(TXB2/6-keto-PGF1α).取心肌组织,电镜下观察病理学结果,进行线粒体损伤评分,并测定线粒体的比表面和面数密度.结果 与S组比较,I/R组血CK-MB、LDH、cTnI、TXB2、6-keto-PGF1α的水平、TXB2/6-keto-PGF1α血小板最大聚集率及线粒体损伤评分升高,线粒体的比表面和面数密度降低(P<0.05或0.01);与I/R组比较,Spr组和Spo组血CK-MB、LDH、cTnI的水平、TXB2/6-keto-PGF1α和线粒体损伤评分降低,血6-keto-PGF1α浓度、线粒体的比表面和面数密度升高(P<0.05或0.01);与Spr组和Spo组比较,Spr+po组血CK-MB、LDH、cTnI、TXB2的水平、TXB2/6-keto-PGF1α血小板最大聚集率和线粒体损伤评分降低,血6-keto-PGF1α浓度、线粒体的比表面和面数密度升高(P<0.05).Spr+po组心肌损伤程度轻于Spr组和Spo组.结论 与七氟醚预处理或后处理比较,两种方法联合应用可抑制血栓素A2的释放和促进前列腺素I2的释放,从而进一步减轻了大鼠心肌缺血再灌注损伤.

Abstract：

Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.     

Prostaglandin E2, prostacyclin, and thromboxane changes during nonpulsatile cardiopulmonary bypass in humans

To study the effect of lung bypass on the production of prostaglandin E2, prostacyclin, and thromboxane A2, we measured simultaneously arterial and venous plasma concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin), and thromboxane B2 (stable metabolite of thromboxane A2) before, during, and after cardiopulmonary bypass. Seventeen patients (age range 46 to 69 years) undergoing aorta-coronary bypass grafts were investigated. The prostaglandin E2 production rose sharply immediately after the onset of bypass (baseline: 9.7 +/- 2.9 pg/ml to 85 +/- 16.6 pg/ml in venous and 87 +/- 12 pg/ml in arterial plasma, p less than 0.03) and rapidly decreased after pulmonary reperfusion (53 +/- 6.4 and 57 +/- 20 pg/ml, respectively, in venous and arterial plasma at the end of bypass). The increase in prostaglandin E2 was influenced by the heart-lung machine itself (as demonstrated by a closed "bypass" circuit) and by lung bypass. Pulmonary metabolism of prostaglandin E2 was maintained after bypass. The prostacyclin production rose significantly at the beginning of bypass (154 +/- 26 pg/ml venous prebypass level to 361 +/- 94 pg/ml after aortic clamping, p less than 0.03). Prostacyclin decreased progressively during rewarming of the patient, pulmonary reperfusion, and discontinuation of bypass. When prostacyclin decreased, thromboxane B2 production rose significantly and reached peak arterial levels when the lungs were reperfused (112 +/- 33 pg/ml prebypass levels to 402 +/- 101 pg/ml, p less than 0.01). Except for prostaglandin E2, there were no significant differences between arterial and venous plasma levels of these substances. The same prostanoids were also measured in five patients undergoing major orthopedic operations, and no significant changes in prostanoids were observed. Our data demonstrate significant production of prostaglandin E2 in the systemic circulation during cardiopulmonary bypass in humans. They further indicate that lung bypass disturbs the plasma prostaglandin/thromboxane balance.     

Effect of experimental cardiopulmonary bypass on systemic and transcardiac thromboxane B2 levels

Systemic and cardiac metabolism of thromboxane was studied in a canine model (n = 13) of standard cardiopulmonary bypass and surgical cardioplegia. Sterile techniques were applied and no donor blood was used. Systemic samples (thoracic aorta) and transcardiac gradients (coronary sinus - aortic root) were obtained (1) 5 minutes after cannulation, (2) 20 minutes after the onset of partial bypass, (3) 5 seconds after the first administration of cardioplegic solution (CP-1), and (4) 5 seconds after the second administration of cardioplegic solution (CP-2). Cardioplegic doses were administered 30 minutes apart and consisted of 500 ml of hypothermic (8 degrees C), hyperkalemic (25 mEq potassium chloride) solution infused into the aortic root at 60 to 70 mm Hg. Thromboxane B2 was determined by a double-antibody radioimmunoassay (picograms per milliliter +/- standard error of the mean). Onset of partial bypass was followed by a significant rise in systemic arterial thromboxane B2 levels: after cannulation, 115 +/- 21 pg/ml; after the onset of partial bypass, 596 +/- 141 pg/ml; p less than 0.01). Significant transcardiac thromboxane B2 gradients were found during the first and second cardioplegic washouts (CP-1: aortic root 73 +/- 12 pg/ml, coronary sinus 306 +/- 86 pg/ml, p less than 0.01; CP-2: aortic root 65 +/- 11 pg/ml, coronary sinus 355 +/- 98 pg/ml, p less than 0.01). Transcardiac gradients of 6-keto-prostaglandin F1 alpha and thromboxane B2 were obtained at CP-1 and CP-2. Gradients of 6-keto-prostaglandin F1 alpha were not different from thromboxane B2 gradients during CP-1 but were significantly higher than thromboxane B2 gradients during CP-2. In a subgroup of five dogs, transcardiac thromboxane B2, lactate, and platelet gradients were measured simultaneously. Cardiac thromboxane B2 generation was found only in the presence of cardiac lactate production. Transcardiac platelet gradients were significantly higher at CP-1 (13,900 +/- 3,000/mm3) than at CP-2 (4,000 +/- 1,230/mm3) (p less than 0.05), whereas thromboxane B2 gradients were similar at CP-1 and CP-2. Our study demonstrates that thromboxane B2 is released into the coronary circulation during surgical cardioplegic arrest with anaerobiosis.     

Pharmacokinetics of tranexamic acid during cardiopulmonary bypass

BACKGROUND: Tranexamic acid (TA) reduces blood loss and blood transfusion during heart surgery with cardiopulmonary bypass (CPB). TA dosing has been empiric because only limited pharmacokinetic studies have been reported, and CPB effects have not been characterized. We hypothesized that many of the published TA dosing techniques would prove, with pharmacokinetic modeling and simulation, to yield unstable TA concentrations. METHODS: Thirty adult patients undergoing elective coronary artery bypass grafting, valve surgery, or repair of atrial septal defect received after induction of anesthesia: TA 50 mg/kg (n = 11), TA 100 mg/kg (n = 10), or TA 10 mg/kg (n = 10) over 15 min, with 1 mg x kg(-1) x hr(-1) maintenance infusion for 10 h. TA was measured in plasma using high performance liquid chromatography. Pharmacokinetic modeling was accomplished using a mixed effects technique. Models of increasing complexity were compared using Schwarz-Bayesian Criterion (SBC). RESULTS: Tranexamic acid concentrations rapidly fell in all three groups. Data were well fit to a 2-compartment model, and adjustments for CPB were supported by SBC. Assuming a body weight of 80 kg, our model estimates V1 = 10.3 l before CPB and 11.9 l during and after CPB; V2 = 8.5 l before CPB and 9.8 l during and after CPB; Cl1 = 0.15 l/s before CPB, 0.11 l/s during CPB, and 0.17 l/s after CPB; and Cl2 = 0.18 l/s before CPB and 0.21 l/s during and after CPB. Based on simulation of previous studies of TA efficacy, we estimate that a 30-min loading dose of 12.5 mg/kg with a maintenance infusion of 6.5 mg x kg(-1) x hr(-1) and 1 mg/kg added to the pump prime will maintain TA concentration greater than 334 microm, and a higher dose based on 30 mg/kg loading dose plus 16 mg x kg(-1) x h(-1) continuous infusion and 2 mg/kg added to the pump prime would maintain TA concentrations greater than 800 microm. CONCLUSIONS: Tranexamic acid pharmacokinetics are influenced by CPB. Our TA pharmacokinetic model does not provide support for the wide range of TA dosing techniques that have been reported. Variation in TA efficacy from study to study and confusion about the optimal duration of TA treatment may be the result of dosing techniques that do not maintain stable, therapeutic TA concentrations.     

Plasma tranexamic acid concentrations during cardiopulmonary bypass

Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1) via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/- 16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time x creatinine concentration interaction (P < 0.001). IMPLICATIONS: A 10 mg/kg initial dose of tranexamic acid followed by an infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The dosing of tranexamic acid may require adjustment for renal insufficiency.