胰岛素强化治疗联合谷氨酰胺对严重烧伤患者营养代谢和炎症反应及血流动力学影响的前瞻性随机对照研究

娄家祺; 厉晔; 崔庆伟; 张盼; 孙晗; 唐浩; 庄梦梦; 孙勇

doi:10.3760/cma.j.cn501120-20210428-00159

胰岛素强化治疗联合谷氨酰胺对严重烧伤患者营养代谢和炎症反应及血流动力学影响的前瞻性随机对照研究

doi: 10.3760/cma.j.cn501120-20210428-00159

徐州医科大学附属淮海医院　　解放军陆军第七十一集团军医院烧伤整形科　　221004

基金项目:

国家自然科学基金面上项目 81772082

详细信息

通讯作者:
孙勇，Email：sunyong_97@163.com

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出版历程
- 收稿日期: 2021-04-28

A prospectively randomized controlled study of the effects of intensive insulin therapy combined with glutamine on nutritional metabolism, inflammatory response, and hemodynamics in severe burn patients

Department of Burns and Plastic Surgery, the 71st Group Army Hospital of PLA Army, Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou 221004, China

Funds:

General Program of National Natural Science Foundation of China 81772082

More Information

Corresponding author: Sun Yong, Email: sunyong_97@163.com

摘要

摘要: 目的探讨胰岛素强化治疗联合谷氨酰胺对严重烧伤患者营养代谢、炎症反应及血流动力学的影响。方法将徐州医科大学附属淮海医院2017年6月—2019年1月收治的32例符合入选标准的严重烧伤患者纳入此前瞻性随机对照研究。按照随机数字表法将患者分为单纯胰岛素常规治疗组、胰岛素常规治疗+谷氨酰胺组、单纯胰岛素强化治疗组与胰岛素强化治疗+谷氨酰胺组，每组8例，各组患者性别依次为男5例、女3例，男4例、女4例，男3例、女5例，男4例、女4例；年龄依次为（35±7）、（36±9）、（33±11）、（38±7）岁。单纯胰岛素常规治疗组患者在常规治疗基础上，采用胰岛素常规治疗控制血糖；胰岛素常规治疗+谷氨酰胺组患者在单纯胰岛素常规治疗组基础上另补充丙氨酰谷氨酰胺14 d以上；单纯胰岛素强化治疗组患者在常规治疗基础上，采用胰岛素强化治疗控制血糖；胰岛素强化治疗+谷氨酰胺组患者在单纯胰岛素强化治疗组基础上另补充丙氨酰谷氨酰胺。分别于治疗1、3、7、14 d，检测4组患者血糖、白蛋白、前白蛋白、白细胞计数、降钙素原和C反应蛋白（CRP）。统计4组患者治疗1、3、7 d心脏指数、每搏量指数（SVI）、全心舒张末期容积指数（GEDVI）、外周血管阻力指数（SVRI）、血管外肺水指数（EVLWI）、肺血管通透性指数（PVPI）。数据处理行Fisher确切概率法检验、单因素方差分析、重复测量方差分析、Bonferroni法。结果 4组患者均顺利完成研究，无退出病例。治疗3、7、14 d，单纯胰岛素强化治疗组［（5.9±1.3）、（5.8±0.6）、（5.5±0.5）mmol/L］和胰岛素强化治疗+谷氨酰胺组患者血糖［（5.9±1.1）、（5.6±1.1）、（5.2±0.8）mmol/L］均明显低于单纯胰岛素常规治疗组［（9.1±0.5）、（8.4±0.9）、（7.4±1.1）mmol/L，P<0.05］。与单纯胰岛素常规治疗组比，胰岛素常规治疗+谷氨酰胺组、单纯胰岛素强化治疗组、胰岛素强化治疗+谷氨酰胺组患者治疗7、14 d白蛋白明显升高（P<0.05）；与胰岛素强化治疗+谷氨酰胺组比，胰岛素常规治疗+谷氨酰胺组、单纯胰岛素强化治疗组患者治疗14 d白蛋白明显降低（P<0.05）。与单纯胰岛素常规治疗组比，胰岛素常规治疗+谷氨酰胺组、单纯胰岛素强化治疗组患者治疗7、14 d前白蛋白明显升高（P<0.05）；与胰岛素强化治疗+谷氨酰胺组比，单纯胰岛素常规治疗组、胰岛素常规治疗+谷氨酰胺组和单纯胰岛素强化治疗组患者治疗1、7、14 d前白蛋白明显降低（P<0.05）。4组患者治疗1、3、7、14 d白细胞计数、降钙素原、CRP组间两两比较差异均无统计学意义（P>0.05）。治疗3、7 d，胰岛素强化治疗+谷氨酰胺组患者心脏指数、SVI、GEDVI、SVRI明显高于单纯胰岛素常规治疗组（P<0.05），EVLWI、PVPI明显低于单纯胰岛素常规治疗组（P<0.05）。结论谷氨酰胺联合胰岛素强化治疗可在患者严重烧伤后改善体内高代谢，减少内源性营养底物的分解与消耗，同时还有助于心功能恢复、维护血流动力学的稳定性。
- 烧伤 /
- 营养支持 /
- 胃肠外营养 /
- 谷氨酰胺 /
- 代谢 /
- 炎症 /
- 细胞因子类 /
- 血流动力学 /
- 胰岛素强化治疗
Abstract: Objective To observe the effects of intensive insulin therapy combined with glutamine on nutritional metabolism, inflammatory response, and hemodynamics in severe burn patients. Methods Thirty-two severe burn patients who met the inclusion criteria and hospitalized in the Affiliated Huaihai Hospital of Xuzhou Medical University from June 2017 to January 2019 were recruited into a prospectively randomized controlled study. According to the random number table, the patients were divided into conventional insulin therapy alone group, conventional insulin therapy+glutamine group, intensive insulin therapy alone group, and intensive insulin therapy+glutamine group, with 8 patients in each group, with genders of 5 males and 3 females, 4 males and 4 females, 3 males and 5 females, 4 males and 4 females, and ages of (35±7), (36±9), (33±11), and (38±7) years, respectively. Patients in conventional insulin therapy alone group were treated with conventional insulin therapy on the basis of routine treatment to control the blood glucose. Patients in conventional insulin therapy+glutamine group were supplemented with alanyl-glutamine for more than 14 days in addition to the treatment in conventional insulin therapy alone group. Patients in intensive insulin therapy alone group were treated with intensive insulin therapy on the basis of routine treatment to control the blood glucose. Patients in intensive insulin therapy+glutamine group were supplemented with alanyl-glutamine in addition to the treatment in intensive insulin therapy alone group. On treatment day (TD) 1, 3, 7, and 14, the blood glucose, albumin, prealbumin, white blood cell count, procalcitonin (PCT), and C-reactive protein (CRP) of patients in the 4 groups were detected. The cardiac index (CI), stroke volume index (SVI), global end-diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), and pulmonary vascular permeability index (PVPI) of patients in the 4 groups on TD 1, 3, and 7 were measured. Data were statistically analyzed with Fisher′s exact probability test, one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni method. Results All patients in the 4 groups successfully completed the study, and there were no withdrawal cases. On TD 3, 7, and 14, the blood glucose of patients in intensive insulin therapy alone group ((5.9±1.3), (5.8±0.6), (5.5±0.5) mmol/L) and intensive insulin therapy+glutamine group ((5.9±1.1), (5.6±1.1), (5.2±0.8) mmol/L) were significantly lower than those in conventional insulin therapy alone group ((9.1±0.5), (8.4±0.9), (7.4±1.1) mmol/L, P<0.05). Compared with those in conventional insulin therapy alone group, the levels of albumin of patients in conventional insulin therapy+glutamine group, intensive insulin therapy alone group, and intensive insulin therapy+glutamine group were significantly increased on TD 7 and 14 (P<0.05). Compared with the level of albumin of patients in intensive insulin therapy+glutamine group, the levels of albumin of patients in conventional insulin therapy+glutamine group and intensive insulin therapy alone group were significantly decreased on TD 14 (P<0.05). Compared with those in conventional insulin therapy alone group, the levels of prealbumin of patients in conventional insulin therapy+glutamine group and intensive insulin therapy alone group were significantly increased on TD 7 and 14 (P<0.05). Compared with those in intensive insulin therapy+glutamine group, the levels of prealbumin of patients in intensive insulin therapy alone group and conventional insulin therapy+glutamine group were significantly decreased on TD 1, 7, and 14 (P<0.05). There were no statistically significant differences in the white blood cell count, PCT, and CRP of patients in the 4 groups in pairwise comparison between groups on TD 1, 3, 7, and 14 (P>0.05). On TD 3 and 7, the levels of cardiac index, SVI, GEDVI, and SVRI of patients in intensive insulin therapy+glutamine group were significantly higher than those in conventional insulin therapy alone group (P<0.05), while the levels of EVLWI and PVPI were significantly lower than those in conventional insulin therapy alone group (P<0.05). Conclusions Glutamine combined with intensive insulin therapy can improve the hypermetabolism in patients after severe burns, reduce the decomposition and consumption of endogenous nutrient substrates, and at the same time help the recovery of cardiac function and maintenance of hemodynamic stability.
- Burns /
- Nutritional support /
- Parenteral nutrition /
- Glutamine /
- Metabolism /
- Inflammation /
- Cytokines /
- Hemodynamics /
- Intensive insulin therapy
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表1 4组严重烧伤患者一般资料比较

组别	例数	性别（例）		年龄（岁，x¯±s）	烧伤面积（%TBSA，x¯±s）		烧伤指数（%TBSA，x¯±s）
组别	例数	男	女	年龄（岁，x¯±s）	总面积	Ⅲ度面积	烧伤指数（%TBSA，x¯±s）
单纯胰岛素常规治疗组	8	5	3	35±7	48±11	28±7	38±6
胰岛素常规治疗+谷氨酰胺组	8	4	4	36±9	46±13	32±6	40±6
单纯胰岛素强化治疗组	8	3	5	33±11	51±8	33±8	42±7
胰岛素强化治疗+谷氨酰胺组	8	4	4	38±7	50±7	29±7	39±4
F值		—		0.285	0.289	1.259	0.763
P值		>0.05		>0.05	>0.05	>0.05	>0.05
注：“—”表示无此统计量值；TBSA为体表总面积

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表2 4组严重烧伤患者治疗各时间点血糖比较（mmol/L，x¯±s）

组别	例数	1 d	3 d	7 d	14 d
单纯胰岛素常规治疗组	8	9.6±1.2	9.1±0.5	8.4±0.9	7.4±1.1
胰岛素常规治疗+谷氨酰胺组	8	8.5±0.8	8.5±0.6	7.1±1.2	6.0±0.9
单纯胰岛素强化治疗组	8	9.3±0.5	5.9±1.3^a	5.8±0.6^a	5.5±0.5^a
胰岛素强化治疗+谷氨酰胺组	8	9.2±0.9	5.9±1.1^a	5.6±1.1^a	5.2±0.8^a
F值		3.137	34.660	18.507	15.933
P值		<0.05	<0.01	<0.01	<0.01
注：成人空腹血糖正常值为3.9~6.1 mmol/L；处理因素主效应，F=49.598，P<0.01；时间因素主效应，F=62.512，P<0.01；两者交互作用，F=5.119，P<0.01；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05

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表3 4组严重烧伤患者治疗各时间点白蛋白比较（g/L，x¯±s）

组别	例数	1 d	3 d	7 d	14 d
单纯胰岛素常规治疗组	8	23.6±	22.4±	24.2±	25.3±
单纯胰岛素常规治疗组	8	5.4	5.6	7.3	3.0
胰岛素常规治疗+谷氨酰胺组	8	24.2±	23.2±	28.4±	30.4±
胰岛素常规治疗+谷氨酰胺组	8	7.2	6.5	3.4^a	3.6^ab
单纯胰岛素强化治疗组	8	23.8±	23.2±	29.1±	31.0±
单纯胰岛素强化治疗组	8	6.3	8.6	1.6^a	2.7^ab
胰岛素强化治疗+谷氨酰胺组	8	24.0±	24.8±	31.4±	36.8±
胰岛素强化治疗+谷氨酰胺组	8	4.1	5.4	2.6^a	2.9^a
F值		0.014	0.169	3.833	19.069
P值		<0.01	<0.01	<0.05	<0.01
注：白蛋白正常值>35 g/L；处理因素主效应，F=5.794，P<0.01；时间因素主效应，F=39.626，P<0.01；两者交互作用，F=3.636，P<0.05；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05；与胰岛素强化治疗+谷氨酰胺组比较，^bP<0.05

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表4 4组严重烧伤患者治疗各时间点前白蛋白比较（mg/L，x¯±s）

组别	例数	1 d	3 d	7 d	14 d
单纯胰岛素常规治疗组	8	154±10^a	113±15	82±9^a	108±8^a
胰岛素常规治疗+谷氨酰胺组	8	151±15^a	118±14	104±13^ab	159±24^ab
单纯胰岛素强化治疗组	8	155±24^a	116±16	108±16^ab	173±43^ab
胰岛素强化治疗+谷氨酰胺组	8	157±20	141±17	129±20	170±58
F值		0.133	5.292	12.632	18.977
P值		<0.01	<0.05	<0.01	<0.01
注：前白蛋白正常值为280~360 mg/L；处理因素主效应，F=14.586，P<0.01；时间因素主效应，F=2.388，P>0.05；两者交互作用，F=17.254，P<0.01；F值、P值为组间各时间点总体比较所得；与胰岛素强化治疗+谷氨酰胺组比较，^aP<0.05；与单纯胰岛素常规治疗组比较，^bP<0.05

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表5 4组严重烧伤患者治疗各时间点白细胞计数比较（×10⁹/L，x¯±s）

组别	例数	1 d	3 d	7 d	14 d
单纯胰岛素常规治疗组	8	20.9±	13.4±	13.3±	13.1±
单纯胰岛素常规治疗组	8	2.8	1.1	0.9	2.6
胰岛素常规治疗+谷氨酰胺组	8	20.2±	13.9±	13.2±	12.2±
胰岛素常规治疗+谷氨酰胺组	8	3.2	2.2	0.7	0.6
单纯胰岛素强化治疗组	8	18.8±	12.6±	14.0±	12.9±
单纯胰岛素强化治疗组	8	7.4	2.0	1.6	1.5
胰岛素强化治疗+谷氨酰胺组	8	20.2±	12.3±	12.7±	13.0±
胰岛素强化治疗+谷氨酰胺组	8	5.6	1.0	1.9	1.4
F值		0.534	1.148	0.793	0.825
P值		<0.01	<0.01	<0.01	<0.01
注：成人白细胞计数正常值为（4.0~10.0）×10⁹/L；处理因素主效应，F=1.593，P>0.05；时间因素主效应，F=47.331，P<0.01；两者交互作用，F=0.173，P>0.05；F值、P值为组间各时间点总体比较所得

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表6 4组严重烧伤患者治疗各时间点降钙素原比较（ng/mL，x¯±s）

组别	例数	1 d	3 d	7 d	14 d
单纯胰岛素常规治疗组	8	6.00±	3.67±	1.07±	0.66±
单纯胰岛素常规治疗组	8	0.56	0.31	0.16	0.32
胰岛素常规治疗+谷氨酰胺组	8	6.12±	3.81±	0.96±	0.94±
胰岛素常规治疗+谷氨酰胺组	8	1.38	0.41	0.17	0.15
单纯胰岛素强化治疗组	8	5.91±	3.62±	0.94±	0.84±
单纯胰岛素强化治疗组	8	0.90	0.26	0.15	0.24
胰岛素强化治疗+谷氨酰胺组	8	5.72±	3.34±	0.99±	0.92±
胰岛素强化治疗+谷氨酰胺组	8	0.67	0.41	0.13	0.32
F值		0.262	2.557	1.057	2.012
P值		<0.01	<0.01	<0.01	<0.01
注：降钙素原正常值为<0.5 ng/mL；处理因素主效应，F=0.318，P>0.05；时间因素主效应，F=998.094，P<0.01；两者交互作用，F=1.018，P>0.05；F值、P值为组间各时间点总体比较所得

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表7 4组严重烧伤患者治疗各时间点C反应蛋白比较（mg/L，x¯±s）

组别	例数	1 d	3 d	7 d	14 d
单纯胰岛素常规治疗组	8	91±34	78±8	71±18	43±10
胰岛素常规治疗+谷氨酰胺组	8	81±23	77±12	65±15	38±14
单纯胰岛素强化治疗组	8	72±23	84±11	75±16	49±20
胰岛素强化治疗+谷氨酰胺组	8	68±15	77±10	70±13	50±25
F值		1.433	0.780	0.508	0.700
P值		<0.01	<0.01	<0.01	<0.01
注：C反应蛋白正常值为0~5 mg/L；处理因素主效应，F=0.806，P>0.05；时间因素主效应，F=40.417，P<0.01；两者交互作用，F=1.748，P>0.05；F值、P值为组间各时间点总体比较所得

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表8 4组严重烧伤患者治疗各时间点心脏指数比较（L·min^-1·m^-2，x¯±s）

组别	例数	1 d	3 d	7 d
单纯胰岛素常规治疗组	8	3.24±0.43	4.67±0.49	6.21±0.68
胰岛素常规治疗+谷氨酰胺组	8	3.13±0.16	5.39±1.14	6.39±1.12
单纯胰岛素强化治疗组	8	3.28±0.33	5.21±0.41	6.32±0.58
胰岛素强化治疗+谷氨酰胺组	8	3.49±0.24	5.82±0.44^a	6.52±0.43^a
F值		1.964	3.799	0.275
P值		<0.01	<0.01	<0.01
注：心脏指数正常值为3.0~5.0 L·min^-1·m^-2；处理因素主效应，F=3.560，P<0.05；时间因素主效应，F=207.235，P<0.01；两者交互作用，F=1.067，P>0.05；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05

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表9 4组严重烧伤患者治疗各时间点每搏量指数比较（mL/m²，x¯±s）

组别	例数	1 d	3 d	7 d
单纯胰岛素常规治疗组	8	32.1±2.3	43.3±7.9	54.8±3.9
胰岛素常规治疗+谷氨酰胺组	8	34.8±7.6	51.2±13.2	55.3±2.6
单纯胰岛素强化治疗组	8	37.1±6.2	45.3±6.7	54.9±3.2
胰岛素强化治疗+谷氨酰胺组	8	32.1±5.2	55.6±5.3^a	61.1±1.5^a
F值		1.462	3.285	8.752
P值		<0.01	<0.05	<0.01
注：每搏量指数正常值为40~60 mL/m²；处理因素主效应，F=4.134，P<0.01；时间因素主效应，F=106.187，P<0.01；两者交互作用，F=2.717，P<0.05；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05

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表10 4组严重烧伤患者治疗各时间点全心舒张末期容积指数比较（mL/m²，x¯±s）

组别	例数	1 d	3 d	7 d
单纯胰岛素常规治疗组	8	618±175	733±124	812±103
胰岛素常规治疗+谷氨酰胺组	8	671±181	803±69	850±121
单纯胰岛素强化治疗组	8	640±192	768±101	841±135
胰岛素强化治疗+谷氨酰胺组	8	651±125	872±77^a	845±112^a
F值		0.076	3.122	0.168
P值		<0.01	<0.05	<0.01
注：全心舒张末期容积指数正常值为600~800 mL/m²；处理因素主效应，F=1.084，P<0.05；时间因素主效应，F=21.610，P<0.01；两者交互作用，F=0.401，P<0.01；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05

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表11 4组严重烧伤患者治疗各时间点外周血管阻力指数比较（dyn·s·cm^-5·m²，x¯±s）

组别	例数	1 d	3 d	7 d
单纯胰岛素常规治疗组	8	2 187±144	1 528±191	988±145
胰岛素常规治疗+谷氨酰胺组	8	2 342±344	1 592±144	1 102±113
单纯胰岛素强化治疗组	8	2 204±223	1 449±133	1 125±103
胰岛素强化治疗+谷氨酰胺组	8	2 201±179	1 783±253^a	1 201±141^a
F值		0.762	4.660	3.850
P值		<0.01	<0.05	<0.05
注：外周血管阻力指数正常值为1 700~2 400 dyn·s·cm^-5·m²；处理因素主效应，F=3.776，P<0.05；时间因素主效应，F=290.214，P<0.01；两者交互作用，F=1.872，P>0.05；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05

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表12 4组严重烧伤患者治疗各时间点血管外肺水指数比较（mL/kg，x¯±s）

组别	例数	1 d	3 d	7 d
单纯胰岛素常规治疗组	8	6.6±0.5	7.2±0.6	7.8±0.5
胰岛素常规治疗+谷氨酰胺组	8	6.3±0.7	6.4±1.3	7.2±0.9
单纯胰岛素强化治疗组	8	6.3±0.4	6.7±0.8	7.4±0.6
胰岛素强化治疗+谷氨酰胺组	8	6.4±0.6	5.7±0.8^a	6.6±0.5^a
F值		0.370	3.998	4.583
P值		<0.05	<0.05	<0.05
注：血管外肺水指数正常值为3~7 mL/kg；处理因素主效应，F=7.278，P<0.01；时间因素主效应，F=13.412，P<0.01；两者交互作用，F=1.418，P>0.05；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05

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表13 4组严重烧伤患者治疗各时间点肺血管通透性指数比较（x¯±s）

组别	例数	1 d	3 d	7 d
单纯胰岛素常规治疗组	8	1.68±0.19	1.62±0.21	1.31±0.22
胰岛素常规治疗+谷氨酰胺组	8	1.63±0.10	1.51±0.17	1.19±0.17
单纯胰岛素强化治疗组	8	1.57±0.21	1.49±0.11	1.17±0.15
胰岛素强化治疗+谷氨酰胺组	8	1.58±0.14	1.31±0.09^a	0.91±0.18^a
F值		0.875	5.328	6.685
P值		<0.05	<0.05	<0.05
注：肺血管通透性指数正常值为1.0~3.0；处理因素主效应，F=10.508，P<0.01；时间因素主效应，F=67.452，P<0.01；两者交互作用，F=1.382，P>0.05；F值、P值为组间各时间点总体比较所得；与单纯胰岛素常规治疗组比较，^aP<0.05