心脏外科停用抑肽酶前后围术期结果比较

A comparison of post-operative results for cardiac patients with and without aprotinin

目的比较2007年12月19日中国食品及药品监督管理局下令心脏外科术中停用抑肽酶前、后心脏手术围术期结果，进一步探讨在心脏外科病人应用抑肽酶的作用及安全性。方法回顾分析停用抑肽酶前、后各6个月的病人资料，所有人选者均在体外循环下行心脏外科手术，年龄均大于18岁。2007年6月19日至2007年12月18日的手术者为抑肽酶组，入选者均在术中应用抑肽酶。2007年12月19日至2008年6月18日手术者为对照组，入选者在术中均未用抑肽酶。比较两组围术期结果，包括术后失血量、输血量、二次开胸发生率、住院病死率及心、脑、肾、肺等重大并发症的发生率。同时进行多因素Logistic回归分析进一步确认初步比较的结果。结果抑肽酶组入选1699例，对照组2225例。抑肽酶组与对照组比较，术后24h出血量[（402．5±267．3）ml对（628．1±378．2）ml，P〈0．001）]、血浆用量[（317．0±746．0）ml对（400．5±724．2）ml，P〈0．001）]、红细胞用量[（2．6±5．8）U对（3．2±5．6）U，P=0．002）]、因出血二次开胸比例（2．0％对3．7％，P=0．002），均显著低于对照组。两组住院病死率差异无统计学意义（0．5％对1．0％，P=0．08）。两组间术后。肾功能不全、肾衰需要透析治疗、低心排出量综合征、神经系统并发症、严重肺部感染、再次气管插管及总并发症的发生率差异均无统计学意义。抑肽酶组延迟拔管发生率（8．8％）低于对照组（10．7％），P=0．04；呼吸机使用时间低于对照组[（18．9±45．0）h对（22．2±53．6）h，P=0．04）]；动脉血气分析氧分压指数（PO2/FiO2）高于对照组[（535．2±221．2）mmHg对（505．8±214．8）mmHg，P〈0．001）。应用多因素Logistic回归分析后，得到的结果与初步比较的结果一致。结论心脏外科手术中使用抑肽酶可以明显降低术后出血量、输血量及因出血二次开胸的发生率，且对术后肺功能有一定的保护作用，但没有增加围术期病死率和重大并发症的发生率。在国内乃至整个亚洲心脏外科病人中是否应该停用抑肽酶还需要进一步研究。

Objective Aprotinin has been suspended in cardiac surgery since risks factors associated with mortality and other adverse events in western literatures. This study was to investigate the effect of aprotinin on short-term outcomes in cardiac surgery in Chinese patients. Methods Two groups of patients who underwent cardiac surgery during equal period just before and after apmtinin was suspended in China. Aprotinin group （n = 1699） was deffined as operations from June 19, 2007 to Dec 18, 2007, when aprotinin was used in all the patients. Control group （n= 2225） was defined as operations from Dec 19, 2007 to June 18, 2008, when aprotinin was not used. Postoperative outcomes between the two groups, including blood loss and transfusion requirement, in-hospital mortality and major adverse outcome events were compared, using univariate analysis and multivariable logistic regression analysis. Results Aprotinin group had less postoperative blood loss, transfusion requirement and reoperation for bleeding as compared with the control group. Application of aprotinin did not increase the risk of in-hospital mortality （0.5 % vs. 1.0%, P = 0.08） and other major adverse events, including renal dysfunction, renal failure requiring dialysis, low cardiac output syndrome （LCOS）, neurological and pulmonary complications. Aprotinin group also had a shorter mechanical ventilation time （ P = 0.04）, a lower rate of delayed mechanical ventilation time （ P = 0.04） and a higher PaO2/FiO2 in the blood gas analysis （ P 〈 0.001 ）, which presented a better respiratory function. Multivariable Logistic regression analysis got identical results with univariate analysis. Conclusion The use of aprotinin in cardiac surgery could reduce blood loss and transfusion requirement significantly, and showed a protective effect on the lungs. In the mean time it did not increase the risk of mortality or major complications. We suggest further studies should be performed to make a decision of continuing or stopping the use of aprotinin in cardiac surgery in Chinese or Asian population.