- 學位論文
在腹腔手術期間比較以羥乙基澱粉輸液Voluven®和乳酸林格氏輸液在組織灌流和凝血功能的差異
Comparison of Voluven® (6% Hydroxyethyl Starch, 130/0.4) and Lactated Ringer's Solution on Perioperative Tissue Perfusion and Coagulation During Major Abdominal Surgery
摘要
中文摘要 研究背景：重大腹腔手術患者尤其因為術前禁食，腸道準備，術中失血，手術創傷刺激水分的散失及麻醉造成的血管擴張影響等等因素，造成某種程度的體液缺失，需要更多的輸液給予。針對手術病患給予輸液治療，藉以維持足夠的血容量，可以保持血液循環的穩定，避免組織灌流不足的缺氧傷害。傳統的輸液治療有晶體輸液和膠體輸液的差別，手術當中的輸液管理使用何種輸液為佳則未有定論。膠體輸液因為可以保持血管內容積較高的滲透壓力，故有較佳的血容擴張效應，減少組織間隙的體液堆積，也認為能因此增進組織灌流；但膠體輸液中的羥乙基澱粉輸液(hydroxyethyl starch, HES)對於凝血功能的影響則為其最被關注的副作用之一。最新型的羥乙基澱粉輸液Voluven® (0.6% HES, 130/0.4)有較小的平均分子量和羥乙基化比率，其血容擴張效應對組織灌流和凝血功能的影響，即為本研究計畫的目標。 研究方法：在接受重大腹部手術的成年病患，隨機分成兩組分別給予Voluven® 或乳酸林格式輸液當作手術當中主要的維持輸液，輸液的速度快慢依據動脈血壓65 - 90 mmHg或中央靜脈壓力8 - 12 mmHg調整。組織灌流的差異分別在T0（誘導後輸液前基準值）、T1（手術開始）、T2（手術開始1小時）和T3（手術結束）等時間監測心律、動脈血壓、中央靜脈壓、心臟輸出量、心搏變異率及中央靜脈血氧濃度。凝血功能的差異分別在T0（誘導後輸液前基準值）、T4（15 mL/kg輸液後）和T5（基準值後24小時）抽血以全血凝血分析儀(Thrombelastography)檢驗。統計檢定方式以多變數分析(ANOVA)比較兩個組別尖的差異，以repeated measures ANOVA比較各個時間點的組織灌流參數與凝血功能參數差異。統計上的顯著差異為 p < 0.05。 研究結果：在40位接受治療並完成追蹤的病患中，兩個輸液組別在性別、年紀、身高、體重、手術種類、手術時間及術前血色素基礎值並無顯著差異。手術期間兩個組別分別輸注Voluven® 1269.2 ± 394.5 mL (HES group)和乳酸林格式輸液1787.9 ± 686.0 mL (LR group)；總輸液量HES group為1498.1 ± 209.4 mL，LR group為2596.2 ± 328.1 mL，有顯著的統計差異(p < 0.001)。術中血液循環穩定度、心臟輸出及中央靜脈血氧濃度兩組則無顯著差異。手術失血量與排尿量則無顯著差異，但在LR group有較高的濃縮紅血球輸注(10 units vs. 0 unit, p = 0.047)。全血凝血分析儀檢測之凝血功能則顯示在Voluven® 15 mL/kg輸注之後，血栓形成時間（R值）縮短(8.8 ± 2.5 vs. 7.5 ± 1.8, p = 0.045)，但血栓硬度(MA振幅)減弱(61.5 ± 8.5 vs. 55.9 ± 7.6, p = 0.034)，Voluven®輸注對R值的影響可持續至24小時(8.8 ± 2.5 vs. 7.4 ± 1.5, p = 0.031)。 研究結論：在重大腹部手術期間，使用新劑型的6%羥乙基澱粉輸液Voluven®顯示和乳酸林格式輸液在組織灌流有相似的治療效果，但使用Voluven®輸液比乳酸林格式輸液有較佳的血容擴張效應，顯著地減少手術中的輸液總量。在凝血功能影響方面，雖對血栓形成時間及硬度有影響，但並沒有臨床上的意義而因此增加手術出血量或濃縮紅血球的輸注需求。試驗結果顯示，Voluven®可以安全地使用於重大腹部手術期間的輸液治療，作為有效的輸液管理選擇。
並列摘要
Abstract Background: In major abdominal surgery, patients are easily suffered from absolute or relative intravascular volume deficits because of preoperative fasting, gastrointestinal preparation, perioperative bleeding, exposure evaporation, third-space losses, and vasodilation after anesthesia. Hypovolemia during surgery has been associated with intraoperative hemodynamic instability and tissue hypoperfusion. Therefore, adequate restoration of intravascular volume is important to fulfill the nutritive role of the circulation. The choice of the ideal fluid management still poses a clinical dilemma. Colloid fluids, such as hydroxyethyl starch (HES) preparations, are commonly used during surgery because of improved volume expansion effect to avoid of tissue edema and enhance tissue perfusion. However, the known adverse effect of hemostatic impairment associated with HES is concerned. The aim of the investigation was to assess the influence of a newly HES preparation (Voluven®, 6% HES, 130/0.4) on tissue perfusion and coagulation in patients undergoing major abdominal surgery, and to compare it with lactated Ringer’s solution (LR). Methods: Forty adults patients undergoing elective major abdominal surgery was randomized to received either Voluven® or lactated Ringer’s solution to keep arterial blood pressure between 65 – 90 mmHg or central venous pressure between 8 -12 mmHg. Tissue perfusion parameters using heart rate, arterial blood pressure, central venous pressure, cardiac index, stroke volume index and central venous oxygen saturation were measured at T0 (baseline), T1 (start of surgery ), T2 (1 hour after start of surgery) and T3 (end of surgery). Coagulation parameters using thrombelastography were measured at T0 (baseline), T4 (after 15 mL/kg fluid transfused) and T5 (24 hours after baseline). Analysis of variance (ANOVA) was applied to detect the significance between groups and repeated measures ANOVA for significance within group. Significance level is p < 0.05. Results: Baseline data were compatible in both groups, including sex, age, height, weight, type and time of procedures, and concentration of preoperative hemoglobin. A total intraoperative fluid administration were 1498.1 ± 209.4 mL and 2596.2 ± 328.1 mL in HES group and LR group, respectively (p < 0.001); including 1269.2 ± 394.5 mL of Voluven® (HES group) and 1787.9 ± 686.0 mL of LR (LR group). The parameters of tissue perfusion, such as hemodynamics and central venous oxygen saturation, did not differ significantly between the two groups. Intraoperative amount of blood loss and urine output were not significant but more red blood transfusion was needed to complete surgery in LR group than HES group (10 units vs. 0 units, p = 0.047). The kinetics of clot formation (clot formation time, R time) significantly increased after 15 mL/kg Voluven® transfused (8.8 ± 2.5 vs. 7.5 ± 1.8, p = 0.045) and lasted until 24 hours (8.8 ± 2.5 vs. 7.4 ± 1.5, p = 0.031). The MA amplitude decreased significantly after 15 mL/kg Voluven® (61.5 ± 8.5 vs. 55.9 ± 7.6, p = 0.034) and recovered to baseline after 24 hours. Conclusion: Intraoperative intravascular volume replacement with the new HES preparation Voluven® was comparable with LR on tissue perfusion; however, Voluven® showed an improved volume expansion effect than LR. Although strength of clot was impaired after Voluven® replacement as detected by TEG, it did not result in clinically significant bleeding during surgery and hence in needs of blood transfusion. Voluven® may be considered as a safe and effective choice of colloid fluid in major abdominal surgery.