Analysis of risk factors of early enteral nutrition intolerance in extremely severe burn patients
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摘要:
目的 探讨特重度烧伤患者早期肠内营养不耐受的危险因素。 方法 采用回顾性病例对照研究。2018年1月—2020年12月，中国科学院大学宁波华美医院收治符合入选标准的76例成年特重度烧伤患者，其中男55例、女21例，年龄（45±11）岁，烧伤总面积62%（52%，82%）体表总面积。根据患者对早期肠内营养耐受与否将患者分为耐受组（47例）和不耐受组（29例），统计2组患者年龄、性别、体重指数、基础疾病、烧伤总面积、Ⅲ度烧伤面积、简明烧伤严重指数（ABSI）评分、入院当天是否使用机械通气、休克期度过是否平稳、喂养前是否呕吐。记录不耐受组患者早期肠内营养不耐受始发时间、持续时间、发生次数及2组患者手术次数、住院天数、伤后2周内是否发生脓毒症、转归情况以及伤后第1、5、9、13天血清超敏C反应蛋白（hs-CRP）、白蛋白、空腹血糖、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、γ-谷氨酰转肽酶（γ-GT）等数据。对数据行独立样本t检验、Mann-Whitney U检验、χ2检验，筛选患者早期肠内营养不耐受的相关因素。对前述相关因素进行单因素和多因素logistic回归分析，筛选患者早期肠内营养不耐受的独立危险因素。 结果 2组患者年龄、性别、体重指数、基础疾病百分比比较，差异无统计学意义（P>0.05）；与耐受组相比，不耐受组患者烧伤总面积、Ⅲ度烧伤面积、ABSI评分、入院当天机械通气百分比、休克期度过不平稳百分比、喂养前呕吐百分比均明显增加（Z=-4.559、-3.378、-4.067，χ2=18.375、23.319、8.339，P<0.01）。不耐受组患者在肠内营养过程中不耐受始发时间为伤后第（9±4）天，持续时间为4（2，6）d，共发生46次。与耐受组相比，不耐受组患者伤后2周内发生脓毒症百分比及死亡百分比均显著升高（χ2=16.571、12.665，P<0.01）。2组患者手术次数及住院天数相近（P>0.05）；而剔除死亡病例，不耐受组患者的住院天数显著多于耐受组（Z=-2.266，P<0.05）。伤后第1天，不耐受组患者空腹血糖、AST水平显著高于耐受组（t=3.070，Z=-3.070，P<0.01）；伤后第5天，2组患者hs-CRP、白蛋白、空腹血糖、ALT、AST、γ-GT水平均相近（P>0.05）；伤后第9天，不耐受组患者hs-CRP水平高于耐受组（t=2.836，P<0.01），ALT、γ-GT水平则低于耐受组（Z=-3.932、-2.052，P<0.05或P<0.01）；伤后第13天，不耐受组患者hs-CRP水平高于耐受组（t=3.794，P<0.01），空腹血糖、ALT、γ-GT水平则低于耐受组（t=-2.176，Z=-2.945、-2.250，P<0.05或P<0.01）。单因素logistic回归分析显示患者烧伤总面积、Ⅲ度烧伤面积、ABSI评分、入院当天行机械通气、休克期度过不平稳、喂养前呕吐和伤后第1天空腹血糖与早期肠内营养不耐受相关（比值比=1.086、1.052、1.775、9.167、12.797、10.125、1.249，95%置信区间=1.045~1.129、1.019~1.085、1.320~2.387、3.132~26.829、4.199~39.000、2.003~51.172、1.066~1.464，P<0.01）。多因素logistic回归分析显示患者烧伤总面积大、休克期度过不平稳、喂养前呕吐和伤后第1天高空腹血糖是特重度烧伤患者发生早期肠内营养不耐受的独立危险因素（比值比=1.073、6.390、9.004、1.246，95%置信区间=1.021~1.128、1.527~26.734、1.134~71.496、1.007~1.540，P<0.05或P<0.01）。 结论 特重度烧伤患者发生早期肠内营养不耐受的百分比较高，与预后不良密切相关。烧伤总面积大、喂养前呕吐、休克期度过不平稳以及伤后第1天高空腹血糖是特重度烧伤患者发生早期肠内营养不耐受的独立危险因素，针对这类患者启动肠内营养前需仔细评估效益与风险，不可盲目追求早期肠内营养。 Abstract:Objective To explore the risk factors of early enteral nutrition intolerance in extremely severe burn patients. Methods A retrospective case-control study was performed. From January 2018 to December 2020, seventy-six adult patients with extremely severe burns who met the inclusion criteria were admitted to Hwa Mei Hospital of University of Chinese Academy of Sciences, including 55 males and 21 females, aged (45±11) years with burns of 62% (52%, 82%) total body surface area. Depending on the patient's tolerance to early enteral nutrition, they were divided into tolerance group (47 patients) and intolerance group (29 patients), and their clinical data were statistically analyzed, including age, sex, body mass index (BMI), underlying disease, total burn area, full-thickness burn area, abbreviated burn severity index (ABSI) score, implementation of mechanical ventilation on the day of admission, stable shock state, vomiting before feeding. The following data were recorded including the onset time, duration length, and frequency of enteral nutrition intolerance of patients in intolerance group, and the number of operations, the length of hospitalization, the occurrence of sepsis within 2 weeks after injury, the outcome, as well as the serum hypersensitive C-reactive protein (hs-CRP), albumin, fasting blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GT) on post burn day (PBD) 1, 5, 9, and 13 of patients in the two groups. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test to screen the related factors of early enteral nutrition intolerance of the patients. Binary univariate and multivariate logistic regression analysis were used to analyze the independent risk factors of early enteral nutrition intolerance of the patients. Results There were no statistically significant differences in age, sex, BMI, and percentage of underlying disease of patients between the two groups (P>0.05). The total burn area, full-thickness burn area, ABSI score, mechanical ventilation percentage on the day of admission, percentage of unstable shock period, percentage of vomiting before feeding of patients in intolerance group were significantly higher than those in tolerance group (Z=-4.559, -3.378, -4.067, χ2=18.375, 23.319, 8.339, P<0.01). In intolerance group, the onset time of intolerance was (9±4) d after injury, and the duration length was 4 (2, 6) d, with a total of 46 times occurred. Compared with tolerance group, the percentage of sepsis and mortality of patients in intolerance group were significantly higher within 2 weeks after injury (χ2=16.571, 12.665, P<0.01). The number of operation and length of hospitalization of patients in the two groups were similar (P>0.05); however the length of hospitalization of patients in the intolerance group was significantly more than that in tolerance group after excluding the death cases (Z=-2.266, P<0.05). On PBD 1, the level of fasting blood glucose and AST of patients in intolerance group were significantly higher than those in tolerance group (t=3.070, Z=-3.070, P<0.01). On PBD 5, the levels of hs-CRP, albumin, fasting blood-glucose, ALT, AST, and γ-GT of patients in the two groups were similar (P>0.05). On PBD 9, the level of hs-CRP of patients in intolerance group was significantly higher than that in tolerance group (t=2.836, P<0.01), and the levels of ALT and γ-GT of patients in intolerance group were significantly lower than those in tolerance group (Z=-3.932, -2.052, P<0.05 or P<0.01). On PBD 13, the level of hs-CRP of patients in intolerance group was significantly higher than that in tolerance group (t=3.794, P<0.01), and the levels of fasting blood glucose, ALT, and γ-GT of patients in intolerance group were significantly lower than those in tolerance group (t=-2.176, Z=-2.945, -2.250, P<0.05 or P<0.01). Binary univariate logistic regression analysis showed that total burn area, full-thickness burn area, ABSI score, implementation of mechanical ventilation on the day of admission, unstable shock period, vomiting before feeding, and fasting blood-glucose on PBD 1 of patients were related to early enteral nutrition intolerance (odds ratio=1.086, 1.052, 1.775, 9.167, 12.797, 10.125, 1.249, 95% confidence interval=1.045 - 1.129, 1.019 - 1.085, 1.320 - 2.387, 3.132 - 26.829, 4.199 - 39.000, 2.003 - 51.172, 1.066 - 1.464, P<0.01). Multivariate logistic regression analysis showed that the large total burn area, unstable shock period, vomiting before feeding, and high fasting blood-glucose on PBD 1 of patients were the independent risk factors of early enteral nutrition intolerance in patients (odds ratio=1.073, 6.390, 9.004, 1.246, 95% confidence interval=1.021 - 1.128, 1.527 - 26.734, 1.134 - 71.496, 1.007 - 1.540, P<0.05 or P<0.01). Conclusions The percentage of early enteral nutrition intolerance is very high in extremely severe burn patients, which is closely related to poor prognosis. Large total burn area, vomiting before feeding, unstable shock phase, high fasting glucose on PBD 1 of patients are the independent risk factors for early enteral nutrition intolerance in extremely severe burn patients. The benefits and risks should be carefully evaluated before starting enteral nutrition in such patients, and early enteral nutrition should not be blindly pursued. -
参考文献
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表1 2组特重度烧伤患者入院早期临床资料比较
组别 例数 性别［例（%）］ 年龄（岁， 体重指数（kg/m2， 基础疾病［例（%）］ 烧伤总面积［%TBSA，M（P25，P75）］ Ⅲ度烧伤面积［%TBSA，M（P25，P75）］ 男 女 是 否 不耐受组 29 21（72.4） 8（27.6） 47±11 25±4 8（27.6） 21（72.4） 85（63，90） 28（16，43） 耐受组 47 34（72.3） 13（27.7） 44±12 24±3 5（10.6） 42（89.4） 60（51，66） 14（5，28） 统计量值 χ2=0.001 t=1.015 t=0.777 χ2=2.536 Z=-4.559 Z=-3.378 P值 0.994 0.313 0.440 0.111 <0.001 0.001 注：TBSA为体表总面积，ABSI为简明烧伤严重指数 
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表2 2组特重度烧伤患者的预后情况比较
组别 例数 伤后2周内发生脓毒症［例（%）］ 手术次数［次，M（P25，P75）］ 住院天数［d，M（P25，P75）］ 转归［例（%）］ 是 否 全组患者 存活患者 死亡 存活 不耐受组 29 19（65.5） 10（34.5） 3（2，5） 34（17，49） 42（35，62） 10（34.5） 19（65.5） 耐受组 47 9（19.1） 38（80.9） 3（1，5） 33（25，47） 34（26，47） 1（2.1） 46（97.9） 统计量值 χ2=16.571 Z=-1.713 Z=-0.262 Z=-2.266 χ2=12.665 P值 <0.001 0.087 0.793 0.023 <0.001
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表3 2组特重度烧伤患者伤后各时间点血清hs-CRP、白蛋白、空腹血糖及肝功能酶学指标比较
组别 例数 hs-CRP（mg/L， 白蛋白（g/L， 伤后第1天 伤后第5天 伤后第9天 伤后第13天 伤后第1天 伤后第5天 伤后第9天 伤后第13天 不耐受组 29 58±38 148±74 203±89 180±68 32±7 30±5 31±4 30±4 耐受组 47 62±45 123±78 155±60 127±52 31±5 30±4 30±4 30±4 统计量值 t=-0.462 t=1.354 t=2.836 t=3.794 t=0.167 t=0.007 t=0.546 t=0.312 P值 0.646 0.180 0.006 <0.001 0.868 0.994 0.587 0.756 注：hs-CRP为超敏C反应蛋白，ALT为丙氨酸转氨酶，AST为天冬氨酸转氨酶，γ-GT为γ-谷氨酰转肽酶
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表4 影响76例特重度烧伤患者早期肠内营养不耐受的单因素logistic回归分析结果
危险因素 回归系数 Wald值 比值比 95%置信区间 P值 烧伤总面积 （%TBSA） 0.083 17.433 1.086 1.045~1.129 <0.001 Ⅲ度烧伤面积 （%TBSA） 0.050 9.903 1.052 1.019~1.085 0.002 ABSI评分（分） 0.574 14.433 1.775 1.320~2.387 <0.001 入院当天机械通气 2.216 16.351 9.167 3.132~26.829 <0.001 休克期度过不平稳 2.549 20.103 12.797 4.199~39.000 <0.001 喂养前呕吐 2.315 7.843 10.125 2.003~51.172 0.005 伤后第1天空腹 血糖（mmol/L） 0.222 7.533 1.249 1.066~1.464 0.006 注：略去伤后第1天天冬氨酸转氨酶差异无统计学意义的指标；ABSI为简明烧伤严重指数
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表5 影响76例特重度烧伤患者早期肠内营养不耐受的多因素logistic回归分析结果
危险因素 回归系数 Wald值 比值比 95%置信区间 P值 烧伤总面积（%TBSA） 0.071 7.729 1.073 1.021~1.128 0.005 休克期度过不平稳 1.855 6.452 6.390 1.527~26.734 0.011 喂养前呕吐 2.198 4.322 9.004 1.134~71.496 0.038 伤后第1天空腹 血糖（mmol/L） 0.220 4.107 1.246 1.007~1.540 0.043 注：略去Ⅲ度烧伤面积、简明烧伤严重指数评分、入院当天机械通气3个差异无统计学意义的指标；TBSA为体表总面积
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脱细胞真皮基质（ADM） 重症监护病房（ICU） 动脉血氧分压（PaO2） 丙氨酸转氨酶（ALT） 白细胞介素（IL） 磷酸盐缓冲液（PBS） 急性呼吸窘迫综合征（ARDS） 角质形成细胞（KC） 反转录-聚合酶链反应（RT-PCR） 天冬氨酸转氨酶（AST） 半数致死烧伤面积（LA50） 全身炎症反应综合征（SIRS） 集落形成单位（CFU） 内毒素/脂多糖（LPS） 超氧化物歧化酶（SOD） 细胞外基质（ECM） 丝裂原活化蛋白激酶（MAPK） 动脉血氧饱和度（SaO2） 表皮生长因子（EGF） 最低抑菌浓度（MIC） 体表总面积（TBSA） 酶联免疫吸附测定（ELISA） 多器官功能障碍综合征（MODS） 转化生长因子（TGF） 成纤维细胞（Fb） 多器官功能衰竭（MOF） 辅助性T淋巴细胞（Th） 成纤维细胞生长因子（FGF） 一氧化氮合酶（NOS） 肿瘤坏死因子（TNF） 3-磷酸甘油醛脱氢酶（GAPDH） 负压伤口疗法（NPWT） 血管内皮生长因子（VEGF） 苏木精-伊红（HE） 动脉血二氧化碳分压（PaCO2） 负压封闭引流（VSD）
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