Desborough Michael J, Oakland Kathryn, Brierley Charlotte, Bennett Sean, Doree Carolyn, Trivella Marialena, Hopewell Sally, Stanworth Simon J, Estcourt Lise J
Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK.
Cochrane Database Syst Rev. 2017 Jul 10;7(7):CD001884. doi: 10.1002/14651858.CD001884.pub3.
Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed.
To examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders.
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017).
We included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children.
We used the standard methodological procedures expected by Cochrane.
We identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial.The GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life. DDAVP versus placebo or no treatmentTrial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups.Compared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).DDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence).Whether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low.DDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence). DDAVP versus placebo or no treatment for people with platelet dysfunctionCompared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence).DDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence).Whether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low. DDAVP versus tranexamic acidCompared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence).Whether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants).No trial reported all-cause mortality.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants). DDAVP versus aprotininCompared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).No trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants).
AUTHORS' CONCLUSIONS: Most of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.
多种手术过程中都会进行输血,但输血的疗效和安全性越来越受到质疑。因此,需要评估去氨加压素(DDAVP;1-去氨基-8-D-精氨酸加压素)等可能减少围手术期失血的药物的疗效。
研究DDAVP减少围手术期失血及非遗传性出血性疾病患者红细胞输血需求的证据。
我们检索了Cochrane图书馆的Cochrane系统评价数据库(2017年第3期)、MEDLINE(1946年起)、Embase(1974年起)、护理学与健康相关文献累积索引数据库(CINAHL,1937年起)、输血证据库(1980年起)以及正在进行的试验数据库(所有检索截至2017年4月3日)。
纳入比较DDAVP与安慰剂或活性对照(如氨甲环酸、抑肽酶)在成人或儿童手术前、手术期间、手术后即刻或侵入性操作后疗效的随机对照试验。
我们采用Cochrane期望的标准方法程序。
我们识别出65项完成的试验(3874名参与者)和4项正在进行的试验。在65项完成的试验中,39项聚焦于成人心脏手术,3项为小儿心脏手术,12项为骨科手术,2项为整形手术,2项为血管手术;7项研究针对其他病症的手术。这些试验在1986年至2016年间开展,11项由制药公司或对试验结果存在商业利益的一方资助。所有结局的GRADE证据质量均为极低至中等。没有试验报告生活质量。
DDAVP与安慰剂或不治疗比较
试验结果显示,由于基线失血量存在较大差异,不同手术类型在红细胞输注总量(低质量证据)和总失血量(极低质量证据)方面存在显著异质性。因此,这些结局未进行合并,而是按亚组报告。
与安慰剂相比,DDAVP可能会略微减少成人心脏手术中的红细胞输注总量(平均差(MD)-0.52单位,95%置信区间(CI)-0.96至-0.08单位;14项试验,957名参与者),但在骨科手术(MD -0.02,95% CI -0.67至0.64单位;6项试验,303名参与者)、血管手术(MD 0.06,95% CI -0.60至0.73单位;2项试验,135名参与者)或肝脏手术(MD -0.47,95% CI -1.27至0.33单位;1项试验,59名参与者)中可能差异不大或无差异。
DDAVP可能导致输血参与者总数差异不大或无差异(风险比(RR)0.96,95% CI 0.86至1.06;25项试验;1806名参与者)(中等质量证据)。
DDAVP是否能减少成人心脏手术(MD -135.24 mL,95% CI -210.80 mL至-59.68 mL;22项试验,1358名参与者)、骨科手术(MD -285.76 mL,95% CI -514.99 mL至-56.53 mL;5项试验,241名参与者)或血管手术(MD -582.00 mL,95% CI -1264.07 mL至100.07 mL;1项试验,44名参与者)的总失血量尚不确定,因为证据质量极低。
DDAVP可能导致全因死亡率(Peto比值比(pOR)1.09,95% CI 0.51至2.34;22项试验,1631名参与者)或血栓形成事件(pOR 1.36,95% CI 0.85至2.16;29项试验,198名参与者)差异不大或无差异(均为低质量证据)。
DDAVP与安慰剂或不治疗用于血小板功能障碍患者比较
与安慰剂相比,DDAVP可能会减少红细胞输注总量(MD -0.65单位,95% CI -1.16至-0.13单位;6项试验,388名参与者)(低质量证据)和总失血量(MD -253.93 mL,95% CI -408.01 mL至-99.85 mL;7项试验,422名参与者)(低质量证据)。
DDAVP可能导致接受红细胞输血的参与者总数差异不大或无差异(RR 0.83,95% CI 0.66至1.04;5项试验,258名参与者)(中等质量证据)。
DDAVP是否会导致全因死亡率(pOR 0.72,95% CI 0.12至4.22;7项试验;422名参与者)或血栓形成事件(pOR 1.58,95% CI 0.60至4.17;7项试验,422名参与者)差异尚不确定,因为证据质量极低。
DDAVP与氨甲环酸比较
与氨甲环酸相比,DDAVP可能会增加输血量(MD 0.6单位,95% CI 0.09至1.11单位;1项试验,40名参与者)和总失血量(MD 142.81 mL,95% CI 79.78 mL至205.84 mL;2项试验,115名参与者)(均为低质量证据)。
DDAVP是否会增加或减少输血参与者总数尚不确定,因为证据质量极低(RR 2.42,95% CI 1.04至5.64;3项试验,135名参与者)。
没有试验报告全因死亡率。
DDAVP是否会导致血栓形成事件差异尚不确定,因为证据质量极低(pOR 2.92,95% CI 0.32至26.83;2项试验,115名参与者)。
DDAVP与抑肽酶比较
与抑肽酶相比,DDAVP可能会增加输血参与者总数(RR 2.41,95% CI 1.45至4.02;1项试验,99名参与者)(中等质量证据)。
没有试验报告输血量或总失血量,唯一一项将死亡率作为结局的试验未报告死亡情况。
DDAVP是否会导致血栓形成事件差异尚不确定,因为证据质量极低(pOR 0.98,95% CI 0.06至15.89;2项试验,152名参与者)。
比较DDAVP与安慰剂得出的大多数证据来自心脏手术,且DDAVP是在体外循环后给药。在接受心脏手术的成人中,红细胞输注量和总失血量的减少幅度较小,可能在临床上并不重要。DDAVP对儿童和接受非心脏手术的患者是否有益尚不清楚。研究人员的一个关键领域是研究DDAVP对血小板功能障碍患者的影响。很少有试验比较DDAVP与氨甲环酸或抑肽酶;因此,我们不确定这些干预措施的相对疗效。