From the Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Centre for Medical Evidence, Decision Integrity & Clinical Impact (MEDICI), Department of Anesthesia & Perioperative Medicine, University of Western Ontario, London, Ontario, Canada.
Anesth Analg. 2018 Sep;127(3):612-621. doi: 10.1213/ANE.0000000000003508.
Postoperative bleeding remains a frequent complication after cardiovascular surgery and may contribute to serious morbidity and mortality. Observational studies have suggested a relationship between low endogenous plasma fibrinogen concentration and increased risk of postoperative blood loss in cardiac surgery. Although the transfusion of fibrinogen concentrate has been increasing, potential benefits and risks associated with perioperative fibrinogen supplementation in cardiovascular surgery are not fully understood.
PubMed, Cochrane Library, Ovid MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure were searched on January 15, 2017, with automated updates searched until February 15, 2018, to identify all randomized controlled trials (RCTs) of fibrinogen concentrate, whether for prophylaxis or treatment of bleeding, in adults undergoing cardiovascular surgery. All RCTs comparing fibrinogen infusion versus any other comparator (placebo/standard of care or another active comparator) in adult cardiovascular surgery and reporting at least 1 predefined clinical outcome were included. The random-effects model was used to calculate risk ratios and weighted mean differences (95% confidence interval [CI]) for dichotomous and continuous variables, respectively. Subgroup analyses by fibrinogen dose and by baseline risk for bleeding were preplanned.
A total of 8 RCTs of fibrinogen concentrate in adults (n = 597) of mixed risk or high risk undergoing cardiovascular surgery were included. Compared to placebo or inactive control, perioperative fibrinogen concentrate did not significantly impact risk of all-cause mortality (risk ratio, 0.41; 95% CI, 0.12-1.38; I = 10%; P = .15). Fibrinogen significantly reduced incidence of allogeneic red blood cell transfusion (risk ratio, 0.64; 95% CI, 0.49-0.83; I = 0%; P = .001). No significant differences were found for other clinical outcomes. Subgroup analyses were unremarkable when analyzed according to fibrinogen dose, time of infusion initiation, mean cardiopulmonary bypass time, and rotational thromboelastometry/fibrinogen temogram use (all P values for subgroup interaction were nonsignificant).
Current evidence remains insufficient to support or refute routine perioperative administration of fibrinogen concentrate in patients undergoing cardiovascular surgery. Fibrinogen concentrate may reduce the need for additional allogeneic blood product transfusion in cardiovascular surgery patients at high risk or with evidence of bleeding. However, no definitive advantage was found for reduction in risk of mortality or other clinically relevant outcomes. The small number of clinical events within existing randomized trials suggests that further well-designed studies of adequate power and duration to measure all-cause mortality, stroke, myocardial infarction, reoperation, and thromboembolic events should be conducted. Future studies should also address cost-effectiveness relative to standard of care.
心血管手术后出血仍是常见并发症，可能导致严重发病率和死亡率。观察性研究表明，内源性血浆纤维蛋白原浓度低与心脏手术后术后失血风险增加有关。尽管纤维蛋白原浓缩物的输注有所增加，但心血管手术围手术期纤维蛋白原补充的潜在益处和风险尚不完全清楚。
于 2017 年 1 月 15 日检索 PubMed、Cochrane 图书馆、Ovid MEDLINE、Embase、Web of Science 和中国国家知识基础设施，自动更新检索至 2018 年 2 月 15 日，以确定所有接受心血管手术的成人接受纤维蛋白原浓缩物（用于预防或治疗出血）的随机对照试验（RCT）。所有比较纤维蛋白原输注与任何其他比较剂（安慰剂/标准护理或另一种活性比较剂）的成人心血管手术 RCT 均纳入，并报告至少 1 个预先定义的临床结局。使用随机效应模型分别计算二分类和连续变量的风险比和加权均数差（95%置信区间[CI]）。按纤维蛋白原剂量和基线出血风险进行了亚组分析。
共纳入 8 项成人（混合风险或高风险）接受心血管手术的纤维蛋白原浓缩物 RCT（n = 597）。与安慰剂或非活性对照相比，围手术期纤维蛋白原浓缩物并未显著影响全因死亡率的风险（风险比，0.41；95%CI，0.12-1.38；I = 10%；P =.15）。纤维蛋白原显著降低同种异体红细胞输血的发生率（风险比，0.64；95%CI，0.49-0.83；I = 0%；P =.001）。其他临床结局无显著差异。按纤维蛋白原剂量、输注起始时间、平均体外循环时间和旋转血栓弹性描记术/纤维蛋白原温度图使用进行亚组分析时，结果无显著差异（所有亚组交互作用的 P 值均无统计学意义）。
目前的证据仍然不足以支持或反驳心血管手术患者常规围手术期使用纤维蛋白原浓缩物。纤维蛋白原浓缩物可能减少高风险或有出血证据的心血管手术患者对额外同种异体血液制品输血的需求。然而，在死亡率或其他临床相关结局的降低方面并未发现明确优势。现有随机试验中临床事件数量较少表明，应进行设计合理、充分、持续时间足够的进一步研究，以测量全因死亡率、卒中和心肌梗死、再次手术和血栓栓塞事件。未来的研究还应考虑与标准护理相比的成本效益。
