| BackgroundFree flap reconstruction is an important part of radical resection of head and neck malignant tumor.Although the failure rate of flap has been significantly reduced with the development of surgery,the consequences of flap loss are still disastrous.Flap vascular crisis is considered to be serious postoperative flap complications and leads to flap failure,and the formation of thrombus was regarded as one of the important causes leading to the vascular crisis.Besides enhance their surgical skills,different scholars have carried out a variety of perioperative antithrombotic schemes,such as the use of aspirin,low-molecular-weight heparin,unfractionated heparin and dextran,in order to prevent postoperative flap thrombosis.The purpose of this systematic review and network meta-analysis was to search the existing literatures and compare the efficacy and safety of different perioperative prophylactic antithrombotic regimens.MethodLiterature retrieval was conducted in MEDLINE,Embase and the Cochrane Library electronic database,as well as other sources to screen and include studies that met our requirements.Data were extracted and integrated from the included studies,and network meta-analysis was conducted using the programming software STATA,based on three flap outcomes which were flap necrosis,flap thrombosis and hematoma formation.The effectiveness and safety of the protocols under different outcomes were comprehensively analyzed through the results of network map,SUCRA value(the surface under the cumulative ranking curve),consistency test,confidence interval forest map,league table and contribution map.ResultA total of 15 studies were included for a systematic review,of which 8(3RCTs and 5 CCTs)were included in the network meta-analysis,involving antithrombotic regimens as followed:(1)aspirin + low-molecular-weight dextran: postoperative aspirin 40 mg p.o.+ low-molecular-weight dextran500 ml i.v.qd for 5 days;(2)low-molecular-weight heparin: postoperative20/40 mg S.C.qd 5 days;(3)No anticoagulant is used;(4)low-molecular-weight dextran 2 days: 500 ml i.v.qd 2 days after surgery;(5)low-molecular-weight dextran 5 days: after anastomosis/postoperative 500 ml i.v.qd 5 days(3-7 days);(6)Aspirin: 325 mg p.o.qd 5 days after surgery;(7)low-molecular-weight heparin + low-molecular-weight dextran: low-molecular-weight dextran 500 ml i.v.qd for 5 days + low-molecular-weight heparin 20 mg S.C.qd for 5 days;(8)prostaglandin E1: postoperative 80mcg/500 m L NS i.v.20ml/h 5-7 days;(9)unfractionated heparin: postoperative low dose of unfractionated heparin500IU/h or 100IU/kg/d i.v.5-7 days;(10)Warfarin: maintain patient’s personal dosage.The study of Warfarin was excluded due to the high risk of heterogeneity.The results of network meta-analysis showed that the three treatment networks based on the outcomes of flap necrosis,flap thrombosis and hematoma formation presented satisfied network structure and acceptable consistency.And aspirin regimen had the highest SUCRA value of 75.8 for the outcome of flap necrosis.In terms of antithrombotic ability,2-day regimen with low-molecular-weight dextran was the best,which SUCRA value was 78.1,followed by aspirin with SUCRA value 74.8;Low-molecular-weight heparin alone was considered to be the least effective in preventing flap necrosis and antithrombotic,with SUCRA values of 23.8 and 21.7 in the two groups,respectively.The 5-day low-molecular-weight dextran regimen ranked the highest with SUCRA value of 90.7,while the low-molecular-weight heparin +low-molecular-weight dextran regimen ranked the lowest with SUCRA value of7.1 in group of hematoma formation.Confidence intervals and league tables for paired comparisons indicated that there was no significant difference between most regimens,but between the comparison of other regimens with low-molecular-weight dextran 5-day or aspirin + low-molecular-weight dextran regimens in the hematoma formation treatment network.The contribution graph showed that each direct comparison on the overall network analysis was well-proportioned,and the direct comparison between no anticoagulant and low-molecular-weight dextran 5-day had the greatest influence on the treatment network of flap necrosis and thrombosis,accounting for 13.7% in the former and 14.7% in the latter.In the treatment network for hematoma formation,the most influential factors were the comparison of low-molecular-weight heparin and no anticoagulant,as well as low-molecular-weight heparin and unfractionated heparin,both accounting for14%.ConclusionPostoperative use of aspirin and low-molecular-weight dextran can effectively reduce the thrombosis of the free flap after head and neck tumor ablative surgery and improve the survival rate of the flap.The postoperative use of low-molecular-weight dextran + low-molecular-weight heparin is also effective in reducing the thrombosis and improving the survival rate of flap.However,this regimen has a higher risk of postoperative hematoma formation among other prophylaxis.The effectiveness of perioperative prophylactic antithrombotic therapy for flap reconstruction after head and neck tumor ablative surgery and the optimal drug regimen need advanced research. |
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