局部柠檬酸抗凝在重症烧伤患者连续性静脉-静脉血液滤过中的效果

王志勇; 冯世海; 范宝莉; 马伟; 贾享成; 耿辉

doi:10.3760/cma.j.cn501120-20200816-00381

局部柠檬酸抗凝在重症烧伤患者连续性静脉-静脉血液滤过中的效果

doi: 10.3760/cma.j.cn501120-20200816-00381

南开大学附属医院（天津市第四医院）烧伤整形科　　300222

基金项目:

天津市自然科学基金项目 19JCYBJC27700

详细信息

通讯作者:
冯世海，Email：fengshihai888@hotmail.com

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出版历程
- 收稿日期: 2020-08-16

Effects of regional citrate anticoagulation in continuous veno-venous hemofiltration of severe burn patients

Department of Burn Plastic Surgery, Affiliated Hospital of Nankai University (the Fourth Hospital of Tianjin) , Tianjin 300222, China

Funds:

Natural Science Foundation of Tianjin 19JCYBJC27700

More Information

Corresponding author: Feng Shihai, Email: fengshihai888@hotmail.com

摘要

摘要: 目的探讨局部柠檬酸抗凝在重症烧伤患者连续性静脉-静脉血液滤过中的效果。方法采用回顾性非随机对照研究。2017年1月—2020年8月，南开大学附属医院收治符合入选标准的重症烧伤患者68例，均行连续性静脉-静脉血液滤过（CVVH）治疗。根据患者在CVVH治疗中采用的血液抗凝方式不同，分为柠檬酸组40例和肝素组28例。柠檬酸组患者中男32例、女8例，年龄（40±18）岁，烧伤总面积（62±14）%体表总面积（TBSA）；肝素组患者中男22例、女6例，年龄（38±16）岁，烧伤总面积（57±20）%TBSA。记录2组患者CVVH治疗0（即刻）、48、96 h时的血清肌酐水平、C反应蛋白（CRP）值、尿素氮水平并根据其水平计算尿素清除指数，记录血小板计数（PLT）及凝血全项中的凝血酶原时间（PT）和活化部分凝血活酶时间（APTT）。记录CVVH治疗96 h内，患者出现严重低钙血症、创面出血加重、非创面的新发生出血等不良反应导致血液滤过受迫性终止的次数。记录患者每日血液净化滤器使用的时长。对数据行χ²检验、重复测量方差分析、独立样本t检验及Bonferroni校正。结果 2组患者治疗0 h血清尿素氮水平、肌酐水平及CRP值比较，差异均无统计学意义（P>0.05）。柠檬酸组患者治疗48、96 h血清尿素氮水平、肌酐水平及CRP值均明显低于肝素组（t=3.366、-2.315、2.942，-2.657、2.011、-2.441，P<0.05），尿素清除指数均显著高于肝素组（t=1.107、2.233，P<0.05）。2组患者治疗0 h的PLT、PT及APTT比较，差异均无统计学意义（P>0.05）。柠檬酸组患者治疗48、96 h的PLT明显高于肝素组（t=-3.417、-4.413，P<0.05或P<0.01）。柠檬酸组患者治疗48、96 h的PT均明显短于肝素组（t=2.760、-3.655，P<0.01），APTT均明显短于肝素组（t=3.719、5.146，P<0.05或P<0.01）。治疗96 h内，柠檬酸组患者中出现1例低钙血症及1例创面出血加重，均导致血液滤过受迫性终止，未出现非创面新发生出血；肝素组患者中未出现低钙血症，但出现7例创面出血加重及2例非创面新发生出血（均在气管切开处），均导致血液滤过受迫性终止。柠檬酸组患者血液净化滤器使用时长为（11.7±4.8）h，明显长于肝素组的（6.6±2.5）h（t=3.310，P<0.01）。结论重症烧伤患者行CVVH治疗时采用局部柠檬酸抗凝具有对患者凝血功能影响小、安全性高等优点，并可效延长滤器使用时间，提升治疗效果，但该结论仍需在临床应用中进一步验证。
- 烧伤 /
- 血液滤过 /
- 抗凝药 /
- 肝素 /
- 柠檬酸 /
- 重症患者
Abstract: Objective To investigate the effects of regional citrate anticoagulation in continuous veno-venous hemofiltration (CVVH) of severe burn patients. Methods A retrospective non-randomized controlled study was conducted. From January 2017 to August 2020, sixty-eight severe burn patients who met the inclusion criteria were treated with CVVH in Affiliated Hospital of Nankai University. According to the different methods of blood anticoagulation in CVVH treatment, patients were divided into citrate group (n=40) and heparin group (n=28). In the citrate group, 32 males and 8 females were (40±18) years old with total burn area of (62±14)% total body surface area (TBSA); in the heparin group, 22 males and 6 females were (38±16) years old with total burn area of (57±20)%TBSA. Creatinine level, C-reactive protein (CRP) value, and urea nitrogen level in serum of patients were recorded at 0 (immediately), 48, and 96 h after CVVH treatment in 2 groups, urea clearance index was calculated based on urea nitrogen level at 0, 48, and 96 h after CVVH treatment in 2 groups, platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) in total coagulation of patients were recorded. The frequency of forced hemofiltration termination caused by adverse reactions such as severe hypocalcemia, aggravated wound bleeding, and new bleeding on non-wound surface of patients was recorded within 96 h of CVVH treatment. The duration of daily CVVH use from the beginning to the end was recorded. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent samples t test, and Bonferroni correction. Results There were no significant differences in urea nitrogen level, creatinine level, and CRP value in serum of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h after treatment, urea nitrogen level, creatinine level, and CRP value in serum of patients in citrate group were significantly lower than those in heparin group (t=3.366, -2.315, 2.942, -2.657, 2.011, -2.441, P<0.05), and urea clearance index of patients in citrate group was significantly higher than that in heparin group (t=1.017, 2.233, P<0.05). There were no statistically significant differences in PLT, PT, and APTT of patients between 2 groups at 0 h after treatment (P>0.05). At 48 and 96 h, PLT of patients in citrate group was significantly higher than that in heparin group (t=-3.417, -4.143, P<0.05 or P<0.01), PT of patients in citrate group was significantly shorter than that in heparin group (t=2.760, -3.655, P<0.01), APTT of patients in citrate group was significantly shorter than that in heparin group (t=3.719, 5.146, P<0.05 or P<0.01). Within 96 h of treatment, there was 1 case of hypocalcemia and 1 case of aggravated wound bleeding resulting in forced hemofiltration termination in citrate group, but there was no new bleeding on non-wound surface; in heparin group, there was no hypocalcemia, but 7 cases of aggravated wound bleeding and 2 cases of new bleeding on non-wound surface (both at the tracheotomy site) resulting in forced hemofiltration termination. The use time of blood purification filter of patients in citrate group was (11.7±4.8) h, obviously longer than (6.6±2.5) h in heparin group (t=3.310, P<0.01). Conclusions The use of regional citrate anticoagulation in CVVH treatment of severe burn patients has the advantages including little effect on coagulation function and high safety, can effectively prolong the use time of filter and improve the therapeutic effect, but this conclusion still needs to be further verified in clinical application.
- Burns /
- Hemofiltration /
- Anticoagulant drugs /
- Heparin /
- Citrate /
- Severe patients
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表1 2组行连续性静脉-静脉血液滤过的重症烧伤患者临床资料比较

组别	例数	性别（例）		年龄（岁，x¯±s）	体重（kg，x¯±s）	烧伤总面积（%TBSA，x¯±s）	Ⅲ度烧伤面积（%TBSA，x¯±s）	血液滤过前APACHEⅡ评分（分，x¯±s）
组别	例数	男	女	年龄（岁，x¯±s）	体重（kg，x¯±s）	烧伤总面积（%TBSA，x¯±s）	Ⅲ度烧伤面积（%TBSA，x¯±s）	血液滤过前APACHEⅡ评分（分，x¯±s）
柠檬酸组	40	32	8	40±18	65±15	62±14	28±14	21±4
肝素组	28	22	6	38±16	67±18	57±20	26±16	22±4
统计量值		χ²=0.265		t=1.252	t=-0.323	t=1.751	t=0.465	t=-0.657
P值		0.790		0.422	0.675	0.216	0.487	0.903
注：TBSA为体表总面积，APACHEⅡ为急性生理学和慢性健康状况评价Ⅱ

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表2 2组行连续性静脉-静脉血液滤过的重症烧伤患者血液滤过效果及血液滤过对凝血功能影响的比较（x¯±s）

组别与时间点	例数	血液滤过效果				对凝血功能的影响
组别与时间点	例数	尿素氮（mmol/L）	肌酐（μmol/L）	CRP（mmol/L）	尿素清除指数	PLT（×10⁹/L）	PT（s）	APTT（s）
柠檬酸组	40
治疗0 h		29.8±3.7	195±41	162±12	－	165±54	10.6±2.2	36±4
治疗48 h		21.4±2.4	138±31	130±18	0.88±0.18	142±58	9.9±2.5	37±3
治疗96 h		18.8±3.0	120±39	98±18	1.07±0.15	130±50	10.4±1.9	36±4
肝素组	28
治疗0 h		29.2±3.1	191±37	157±11	－	158±57	11.2±2.0	35±5
治疗48 h		25.6±2.8	156±28	148±16	0.74±0.09	120±63	15.3±2.8	46±4
治疗96 h		22.3±2.8	141±34	120±15	0.80±0.12	91±57	19.1±3.4	51±6
t₁值		3.073	2.460	3.948	－	2.745	-1.544	1.904
P₁值		0.446	0.188	0.081	－	0.130	0.359	0.331
t₂值		3.366	-2.315	2.942	1.017	-3.417	2.760	3.719
P₂值		0.021	0.040	0.035	0.020	0.024	0.004	0.017
t₃值		-2.657	2.011	-2.441	2.233	-4.143	-3.655	5.146
P₃值		0.020	0.025	0.018	0.012	0.005	0.002	0.006
注：CRP为C反应蛋白，PLT为血小板计数，PT为凝血酶原时间，APTT为活化部分凝血活酶时间；“－”表示无此项；尿素氮处理因素主效应，F=13.582，P=0.022；时间因素主效应，F=6.725，P=0.034；两者交互作用，F=9.508，P=0.028；肌酐处理因素主效应，F=6.767，P=0.030；时间因素主效应，F=8.258，P=0.037；两者交互作用，F=5.442，P=0.024；CRP处理因素主效应，F=7.732，P=0.022；时间因素主效应，F=12.755，P=0.025；两者交互作用，F=4.197，P=0.027；尿素清除指数处理因素主效应，F=5.301，P=0.037；时间因素主效应，F=10.697，P=0.029；两者交互作用，F=3.667，P=0.031；PLT处理因素主效应，F=22.273，P=0.017；时间因素主效应，F=10.630，P=0.028；两者交互作用，F=8.411，P=0.025；PT处理因素主效应，F=6.003，P=0.098；时间因素主效应，F=5.563，P=0.031；两者交互作用，F=4.978，P=0.029；APTT处理因素主效应，F=6.602，P=0.104；时间因素主效应，F=5.715，P=0.045；两者交互作用，F=6.729，P=0.038；t₁值、P₁值，t₂值、P₂值，t₃值、P₃值分别为2组患者治疗0（即刻）、48、96 h各指标比较所得