儿童危重症应激性高血糖对器官功能的影响

doi:10.12372/jcp.2022.23e0258

摘要/Abstract

摘要：

重症患儿在应激状态下可出现应激性高血糖（SHG）。目前认为SHG的发病机制与危重症时的内分泌激素调节异常、细胞因子大量释放以及胰岛素抵抗相关。血糖水平持续增高可引起线粒体功能障碍、炎症途径激活和氧化应激。近年来，虽然SHG与不良预后之间的相关性受到广泛关注，但严格控制血糖联合强化胰岛素治疗的策略似乎并不能让重症儿童获益，总体而言，血糖不超过180 mg/dL（10.0 mmol/L）为宜。文章梳理SHG的定义、发病机制及对机体的危害等方面的研究进展，以期提高临床医师认识。

关键词: 应激性高血糖, 危重病, 儿童

Abstract:

Stress-induced hyperglycemia (SHG) may occur in severe children under stress. It is currently believed that the pathogenesis of SHG is related to abnormal regulation of endocrine hormones, massive release of cytokines, and insulin resistance in critical cases. Continuous elevated blood glucose levels can cause mitochondrial dysfunction, activation of inflammatory pathways, and oxidative stress. Although the association between SHG and poor prognosis has received widespread attention in recent years, strategies to strictly control blood glucose combined with intensive insulin therapy do not seem to benefit critically ill children. In general, blood glcose not exceeding 180 mg/dL （10.0 mmol/L） is appropriate. This article reviews the progress of research on the definition, pathogenesis and harm of SHG in order to improve clinicians’ understanding.

Key words: stress hyperglycemia, critically ill, child

武洁, 王荃. 儿童危重症应激性高血糖对器官功能的影响[J]. 临床儿科杂志, 2023, 41(6): 406-410.

WU Jie, WANG Quan. Effects of stress hyperglycemia on organ function in critically ill children[J]. Journal of Clinical Pediatrics, 2023, 41(6): 406-410.

参考文献 43

[1]	Faustino EV, Apkon M. Persistent hyperglycemia in critically ill children[J]. J Pediatr, 2005, 146(1): 30-34.
[2]	Dungan KM, Braitwaite SS, Preiser JC. Stress hyperglycaemia[J]. Lancet, 2009, 373(9677): 1798-1807. doi: 10.1016/S0140-6736(09)60553-5 pmid: 19465235
[3]	Kerby JD, Griffin RL, MacLennan P, et al. Stress-induced hyperglycemia, not diabetic hyperglycemia, is associated with higher mortality in trauma[J]. Ann Surg, 2012, 256(3): 446-452. doi: 10.1097/SLA.0b013e3182654549 pmid: 22868366
[4]	Srinivasan V. Glucose metabolism and stress hyper-glycemia in critically ill children[J]. Indian J Pediatr, 2023, 90(3): 272-279. doi: 10.1007/s12098-022-04439-y pmid: 36645581
[5]	Yung M, Wilkins B, Norton L, et al. Glucose control, organ failure, and mortality in pediatric intensive care[J]. Pediatr Crit Care Med, 2008, 9(2): 147-152. doi: 10.1097/PCC.0b013e3181668c22
[6]	Li Y, Bai Z, Li M, et al. U-shaped relationship between early blood glucose and mortality in critically ill children[J]. BMC Pediatr, 2015, 15: 88. doi: 10.1186/s12887-015-0403-y pmid: 26204931
[7]	中国医师协会儿科学分会内分泌遗传代谢学组, 中华医学会儿科学分会急救学组. 儿童及青少年特殊情况下住院高血糖管理指导建议[J]. 中华糖尿病杂志, 2020, 12(10): 765-771.
[8]	Srinivasan V. Stress hyperglycemia in pediatric critical illness: the intensive care unit adds to the stress![J]. J Diabetes Sci Technol, 2012, 6(1): 37-47. doi: 10.1177/193229681200600106 pmid: 22401321
[9]	Bhisitkul DM, Morrow AL, Vinik AI, et al. Prevalence of stress hyperglycemia among patients attending a pediatric emergency department[J]. J Pediatr, 1994, 124(4): 547-551. doi: 10.1016/S0022-3476(05)83132-4
[10]	Dufour S, Lebon V, Shulman GI, et al. Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans[J]. Am J Physiol Endocrinol Metab, 2009, 297(1): E231-E235. doi: 10.1152/ajpendo.00222.2009
[11]	Mechanick JI. Metabolic mechanisms of stress hyper-glycemia[J]. JPEN J Parenter Enteral Nutr, 2006, 30(2): 157-163. pmid: 16517960
[12]	Shamoon H, Hendler R, Sherwin RS. Synergistic interactions among antiinsulin hormones in the patho-genesis of stress hyperglycemia in humans[J]. J Clin Endocrinol Metab, 1981, 52(6): 1235-1241. doi: 10.1210/jcem-52-6-1235
[13]	Saini V. Molecular mechanisms of insulin resistance in type 2 diabetes mellitus[J]. World J Diabete, 2010, 1(3): 68-75. doi: 10.4239/wjd.v1.i3.68
[14]	Jeschke MG, Finnerty CC, Herndon DN, et al. Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response[J]. Ann Surg, 2012, 255(2): 370-378. doi: 10.1097/SLA.0b013e31823e76e7 pmid: 22241293
[15]	Boroni Moreira AP, de Cássia Gonçalves Alfenas R. The influence of endotoxemia on the molecular mechanisms of insulin resistance[J]. Nutr Hosp, 2012, 27(2): 382-390. doi: 10.1590/S0212-16112012000200007 pmid: 22732959
[16]	Gardelis JG, Hatzis TD, Stamogiannou LN, et al. Activity of the growth hormone/insulin-like growth factor-I axis in critically ill children[J]. J Pediatr Endocrinol Metab, 2005, 18(4): 363-372. pmid: 15844470
[17]	Li L, Thompson LH, Zhao L, et al. Tissue-specific difference in the molecular mechanisms for the development of acute insulin resistance after injury[J]. Endocrinology, 2009, 150(1): 24-32. doi: 10.1210/en.2008-0742 pmid: 18801909
[18]	曹相原. 血糖控制[M]//杜斌, 隆云. 危重症医学. 3版. 北京: 人民卫生出版社, 2021: 443-453.
[19]	Preissig CM, Rigby MR. Hyperglycemia results from beta-cell dysfunction in critically ill children with respiratory and cardiovascular failure: a prospective observational study[J]. Crit Care, 2009, 13(1): R27. doi: 10.1186/cc7732
[20]	Srinivasan V, Spinella PC, Drott HR, et al. Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children[J]. Pediatr Crit Care Med, 2004, 5(4): 329-336. doi: 10.1097/01.PCC.0000128607.68261.7C
[21]	Ulate KP, Lima Falcao GC, Bielefeld MR, et al. Strict glycemic targets need not be so strict: a more permissive glycemic range for critically ill children[J]. Pediatrics, 2008, 122(4): 898-904. doi: 10.1542/peds.2008-0871 pmid: 18779254
[22]	Hebbard GS, Sun WM, Dent J, et al. Hyperglycemia affects proximal gastric motor and sensory function in normal subjects[J]. Eur J Gastroenterol Hepatol, 1996, 8(3): 211-217. doi: 10.1097/00042737-199603000-00005
[23]	Petrakis IE, Kogerakis N, Prokopakis G, et al. Hyperglycemia attenuates erythromycin-induced acceleration of liquid-phase gastric emptying of hypertonic liquids in healthy subjects[J]. Dig Dis Sci, 2002, 47(1): 67-72. doi: 10.1023/A:1013211419605
[24]	Gore DC, Chinkes DL, Hart DW, et al. Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients[J]. Crit Care Med, 2002, 30(11): 2438-2442. pmid: 12441751
[25]	Kovár J, Fejfarová V, Pelikánová T, et al. Hyperglycemia downregulates total lipoprotein lipase activity in humans[J]. Physiol Res, 2004, 53(1): 61-68. pmid: 14984315
[26]	Baker EH, Wood DM, Brennan AL, et al. Hyperglycaemia and pulmonary infection[J]. Proc Nutr Soc, 2006, 65(3): 227-235. doi: 10.1079/PNS2006499
[27]	Stevens RD, Dowdy DW, Michaels RK, et al. Neuro-muscular dysfunction acquired in critical illness: a systematic review[J]. Intensive Care Med, 2007, 33(11): 1876-1891. doi: 10.1007/s00134-007-0772-2
[28]	El-Sherbini SA, Marzouk H, El-Sayed, et al. Etiology of hyperglycemia in critically ill children and the impact of organ dysfunction[J]. Rev Bras Ter Intensiva, 2018, 30(3): 286-293.
[29]	Rovegno M, Soto PA, Sáez JC, et al. Biological mechanisms involved in the spread of traumatic brain damage[J]. Med Intensiva, 2012, 36(1): 37-44. doi: 10.1016/j.medin.2011.06.008 pmid: 21903299
[30]	Turina M, Fry DE, Polk HC Jr. Acute hyperglycemia and the innate immune system: clinical, cellular, and molecular aspects[J]. Crit Care Med, 2005, 33(7): 1624-1633. doi: 10.1097/01.ccm.0000170106.61978.d8 pmid: 16003073
[31]	Bavisetty S, Bavisetty S, McArthur DL, et al. Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome[J]. Neurosurgery, 2008, 62(5): 1080-1093. doi: 10.1227/01.neu.0000325870.60129.6a pmid: 18580806
[32]	Kinoshita K, Kraydieh S, Alonso O, et al. Effect of posttraumatic hyperglycemia on contusion volume and neutrophil accumulation after moderate fluid-percussion brain injury in rats[J]. J Neurotrauma, 2002, 19(6): 681-692. doi: 10.1089/08977150260139075
[33]	Ellger B, Langouche L, Richir M, et al. Modulation of regional nitric oxide metabolism: blood glucose control or insulin?[J]. Intensive Care Med, 2008, 34(8): 1525-1533. doi: 10.1007/s00134-008-1118-4
[34]	Agus MS, Steil GM, Wypij D, et al. Tight glycemic control versus standard care after pediatric cardiac surgery[J]. N Engl J Med, 2012, 367(13): 1208-1219. doi: 10.1056/NEJMoa1206044
[35]	Tsai YW, Wu SC, Huang CY, et al. Impact of stress-induced hyperglycemia on the outcome of children with trauma: a cross-sectional analysis based on propensity score-matched population[J]. Sci. Rep, 2019, 9(1): 16311. doi: 10.1038/s41598-019-52928-6
[36]	Bae W, Ahn MB. Association between stress hyperglycemia and adverse outcomes in children visiting the pediatric emergency department[J]. Children (Basel), 2022, 9(4): 505.
[37]	Michaud LJ, Rivara FP, Longstreth WT Jr, et al. Elevated initial blood glucose levels and poor outcome following severe brain injuries in children[J]. J Trauma, 1991, 31(10): 1356-1362. doi: 10.1097/00005373-199110000-00007
[38]	Vlasselaers D, Milants I, Desmet L, et al. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study[J]. Lancet, 2009, 373(9663): 547-556. doi: 10.1016/S0140-6736(09)60044-1 pmid: 19176240
[39]	Macrae D, Grieve R, Allen E, et al. A randomized trial of hyperglycemic control in pediatric intensive care[J]. N Engl J Med, 2014, 370(2): 107-118. doi: 10.1056/NEJMoa1302564
[40]	Agus MS, Wypij D, Hirshberg EL, et al. Tight glycemic control in critically Ⅲ children[J]. N Engl J Med, 2017, 376(8): 729-741. doi: 10.1056/NEJMoa1612348
[41]	中国医师协会急诊医师分会. 中国急诊感染性休克临床实践指南[J]. 中华急诊医学杂志, 2016, 25(3): 274-287.
[42]	中华医学会重症医学分会. 中国严重脓毒症/脓毒性休克治疗指南(2014)[J]. 中华内科杂志, 2015, 54(6): 557-581.
[43]	Weiss SL, Peters MJ, Alhazzani W, et al. Executive summary: surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children[J]. Pediatr Crit Care Med, 2020, 21(2): 186-195. doi: 10.1097/PCC.0000000000002197