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ABSTRACT Objective: The purpose of present study was to comprehensively explore the efficacy and safety of prothrombin complex concentrate (PCC) to treat massive bleeding in patients undergoing cardiac surgery. Methods: PubMed®, Embase, and Cochrane Library databases were searched for studies investigating PCC administration during cardiac surgery published before September 10, 2022. Mean difference (MD) with 95% confidence interval (CI) was applied to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. Results: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not associated with elevated mortality (RR=1.18, 95% CI=0.86–1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62–1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52–103.65, P=0.44, I2=91%), thromboembolic events (RR=1.10, 95% CI=0.74–1.65, P=0.63, I2=39%), increase in atrial fibrillation events (RR=0.73, 95% CI=0.52–1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80–1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48– -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36– -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42–0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. Conclusion: The use of PCC in cardiac surgery did not correlate with mortality, length of hospital stay, thoracic drainage, atrial fibrillation, myocardial infarction, and thromboembolic events. However, PCC significantly improved postoperative intensive care unit length of stay, bleeding, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes in patients undergoing cardiac surgery. Objective (PCC Methods PubMed PubMed® Embase 10 2022 MD (MD 95 CI (CI RR (RR Results metaanalysis. metaanalysis meta analysis. analysis meta-analysis nonPCC non regimens RR=1.18, RR118 1 18 (RR=1.18 CI086160 0 86 60 CI=0.86–1.60 P030 P 30 P=0.30 I2=0%, I20 I I2=0% , I2 MD=2.17 MD217 MD= 2.17 2 17 (MD=-2.1 days CI=5.62–1.28, CI562128 CI= 5.62–1.28, 5 62 28 CI=-5.62–1.28 P022 22 P=0.22 I2=91%, I291 I2=91% 91 I2=91%) MD=67.94 MD6794 67.94 67 94 (MD=-67.9 ml CI=239.52–103.65, CI2395210365 239.52–103.65, 239 52 103 65 CI=-239.52–103.65 P044 44 P=0.44 RR=1.10, RR110 (RR=1.10 CI074165 74 CI=0.74–1.65 P063 63 P=0.63 I2=39%, I239 I2=39% 39 I2=39%) RR=0.73, RR073 73 (RR=0.73 CI052105 05 CI=0.52–1.05 P024 24 P=0.24 I2=29%, I229 I2=29% 29 I2=29%) CI080151 80 51 CI=0.80–1.51 P057 57 P=0.57 I2=81%. I281 I2=81% . 81 I2=81%) However MD=0.81 MD081 0.81 (MD=-0.8 CI=1.48– CI148 1.48– 48 CI=-1.48 0.13, 013 13 -0.13 P002 02 P=0.02 MD=248.67 MD24867 248.67 248 (MD=-248.6 CI=465.36– CI46536 465.36– 465 36 CI=-465.36 31.97, 3197 31 97 -31.97 I2=84%, I284 I2=84% 84 I2=84%) intraaortic intra aortic pumpextracorporeal pump RR=0.65, RR065 (RR=0.65 CI0420996 42 996 CI=0.42–0.996 P005 P=0.05 Conclusion 202 9 RR=1.18 RR11 (RR=1.1 CI08616 8 6 CI=0.86–1.6 P03 3 P=0.3 I2=0 MD=2.1 MD21 217 2.1 (MD=-2. CI=5.62–1.28 CI56212 562128 5.62–1.28 CI=-5.62–1.2 P02 P=0.2 I29 I2=91 MD=67.9 MD679 6794 67.9 (MD=-67. CI=239.52–103.65 CI239521036 2395210365 239.52–103.65 23 CI=-239.52–103.6 P04 4 P=0.4 RR=1.10 CI07416 7 CI=0.74–1.6 P06 P=0.6 I23 I2=39 RR=0.73 RR07 (RR=0.7 CI05210 CI=0.52–1.0 I22 I2=29 CI08015 CI=0.80–1.5 P05 P=0.5 I28 I2=81 MD=0.8 MD08 081 0.8 (MD=-0. CI=1.48 CI14 148 1.48 CI=-1.4 0.13 01 -0.1 P00 P=0.0 MD=248.6 MD2486 24867 248.6 (MD=-248. CI=465.36 CI4653 46536 465.36 46 CI=-465.3 31.97 319 -31.9 I2=84 RR=0.65 RR06 (RR=0.6 CI042099 99 CI=0.42–0.99 20 RR=1.1 RR1 (RR=1. CI0861 CI=0.86–1. P0 P=0. I2= MD=2. MD2 21 2. (MD=-2 CI=5.62–1.2 CI5621 56212 5.62–1.2 CI=-5.62–1. I2=9 MD=67. MD67 679 67. (MD=-67 CI=239.52–103.6 CI23952103 239521036 239.52–103.6 CI=-239.52–103. CI0741 CI=0.74–1. I2=3 RR=0.7 RR0 (RR=0. CI0521 CI=0.52–1. I2=2 CI0801 CI=0.80–1. I2=8 MD=0. MD0 08 0. (MD=-0 CI=1.4 CI1 14 1.4 CI=-1. 0.1 -0. MD=248. MD248 2486 248. (MD=-248 CI=465.3 CI465 4653 465.3 CI=-465. 31.9 -31. RR=0.6 CI04209 CI=0.42–0.9 RR=1. (RR=1 CI086 CI=0.86–1 P=0 MD=2 (MD=- CI=5.62–1. CI562 5621 5.62–1. CI=-5.62–1 MD=67 MD6 (MD=-6 CI=239.52–103. CI2395210 23952103 239.52–103. CI=-239.52–103 CI074 CI=0.74–1 RR=0. (RR=0 CI052 CI=0.52–1 CI080 CI=0.80–1 MD=0 CI=1. 1. CI=-1 -0 MD=248 MD24 (MD=-24 CI=465. CI46 465. CI=-465 31. -31 CI0420 CI=0.42–0. RR=1 (RR= CI08 CI=0.86– P= (MD= CI=5.62–1 CI56 562 5.62–1 CI=-5.62– MD=6 CI=239.52–103 CI239521 2395210 239.52–103 CI=-239.52–10 CI07 CI=0.74– RR=0 CI05 CI=0.52– CI=0.80– CI=1 CI=- - MD=24 CI=465 CI4 CI=-46 -3 CI042 CI=0.42–0 RR= CI0 CI=0.86 CI=5.62– CI5 56 5.62– CI=-5.62 CI=239.52–10 CI23952 239521 239.52–10 CI=-239.52–1 CI=0.74 CI=0.52 CI=0.80 CI=46 CI=-4 CI04 CI=0.42– CI=0.8 CI=5.62 5.62 CI=-5.6 CI=239.52–1 CI2395 23952 239.52–1 CI=-239.52– CI=0.7 CI=0.5 CI=4 CI=0.42 CI=0. CI=5.6 5.6 CI=-5. CI=239.52– CI239 2395 239.52– CI=-239.52 CI=0.4 CI=0 CI=5. 5. CI=-5 CI=239.52 CI23 239.52 CI=-239.5 CI=5 CI=239.5 CI2 239.5 CI=-239. CI=239. 239. CI=-239 CI=239 CI=-23 CI=23 CI=-2 CI=2