Fisher Jeremy G, Sparks Eric A, Khan Faraz A, Alexander Jamin L, Asaro Lisa A, Wypij David, Gaies Michael, Modi Biren P, Duggan Christopher, Agus Michael S D, Yu Yong-Ming, Jaksic Tom
1Center for Advanced Intestinal Rehabilitation and Department of Surgery, Boston Children's Hospital, Boston, MA. 2Harvard Medical School, Boston, MA. 3Division of Medicine Critical Care, Boston Children's Hospital, Boston, MA. 4Department of Cardiology, Boston Children's Hospital, Boston, MA. 5Department of Biostatistics, Harvard School of Public Health, Boston, MA. 6Division of Pediatric Cardiology, C.S. Mott Children's Hospital and University of Michigan Medical School, Ann Arbor, MI. 7Center for Advanced Intestinal Rehabilitation and Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA. 8Shriners Hospital for Children and Massachusetts General Hospital, Boston, MA.
Pediatr Crit Care Med. 2015 Jul;16(6):515-21. doi: 10.1097/PCC.0000000000000413.
Critical illness is associated with significant catabolism, and persistent protein loss correlates with increased morbidity and mortality. Insulin is a potent anticatabolic hormone; high-dose insulin decreases skeletal muscle protein breakdown in critically ill pediatric surgical patients. However, insulin's effect on protein catabolism when given at clinically utilized doses has not been studied. The objective was to evaluate the effect of postoperative tight glycemic control and clinically dosed insulin on skeletal muscle degradation in children after cardiac surgery with cardiopulmonary bypass.
Secondary analysis of a two-center, prospective randomized trial comparing tight glycemic control with standard care. Randomization was stratified by study center.
Children 0-36 months who were admitted to the ICU after cardiac surgery requiring cardiopulmonary bypass.
In the tight glycemic control arm, insulin was titrated to maintain blood glucose between 80 and 110 mg/dL. Patients in the control arm received standard care. Skeletal muscle breakdown was quantified by a ratio of urinary 3-methylhistidine to urinary creatinine.
A total of 561 patients were included: 281 in the tight glycemic control arm and 280 receiving standard care. There was no difference in 3-methylhistidine to creatinine between groups (tight glycemic control, 249 ± 127 vs standard care, 253 ± 112, mean ± SD in μmol/g; p = 0.72). In analyses restricted to the patients in tight glycemic control arm, higher 3-methylhistidine to creatinine correlated with younger age, as well as lower weight, weight-for-age z score, length, and body surface area (p < 0.005 for each) and lower postoperative day 3 serum creatinine (r = -0.17; p = 0.02). Sex, prealbumin, and albumin were not associated with 3-methylhistidine to creatinine. During urine collection, 245 patients (87%) received insulin. However, any insulin exposure did not impact 3-methylhistidine to creatinine (t test, p = 0.45), and there was no dose-dependent effect of insulin on 3-methylhistidine to creatinine (r = -0.03; p = 0.60).
Although high-dose insulin has an anabolic effect in experimental conditions, at doses necessary to achieve normoglycemia, insulin appears to have no discernible impact on skeletal muscle degradation in critically ill pediatric cardiac surgical patients.
危重症与显著的分解代谢相关，持续性蛋白质丢失与发病率和死亡率增加相关。胰岛素是一种强效的抗分解代谢激素；高剂量胰岛素可降低危重症小儿外科手术患者的骨骼肌蛋白质分解。然而，临床常用剂量胰岛素对蛋白质分解代谢的影响尚未得到研究。本研究目的是评估术后严格血糖控制及临床剂量胰岛素对体外循环心脏手术后儿童骨骼肌降解的影响。
对一项比较严格血糖控制与标准治疗的两中心前瞻性随机试验进行二次分析。随机分组按研究中心分层。
0至36个月在体外循环心脏手术后入住重症监护病房（ICU）的儿童。
在严格血糖控制组，滴定胰岛素以维持血糖在80至110mg/dL之间。对照组患者接受标准治疗。通过尿3 - 甲基组氨酸与尿肌酐的比值对骨骼肌分解进行量化。
共纳入561例患者：严格血糖控制组281例，接受标准治疗组280例。两组间3 - 甲基组氨酸与肌酐的比值无差异（严格血糖控制组，249±127；标准治疗组，253±112，单位为μmol/g，均值±标准差；p = 0.72）。在仅限于严格血糖控制组患者的分析中，较高的3 - 甲基组氨酸与肌酐比值与年龄较小、体重较低、年龄别体重z评分较低、身长和体表面积较低相关（每项p < 0.005），且与术后第3天血清肌酐较低相关（r = -0.17；p = 0.02）。性别、前白蛋白和白蛋白与3 - 甲基组氨酸与肌酐的比值无关。在尿液收集期间，245例患者（87%）接受了胰岛素治疗。然而，任何胰岛素暴露均未影响3 - 甲基组氨酸与肌酐的比值（t检验，p = 0.45），且胰岛素对3 - 甲基组氨酸与肌酐的比值无剂量依赖性影响（r = -0.03；p = 0.60）。
尽管高剂量胰岛素在实验条件下具有合成代谢作用，但在实现血糖正常所需的剂量下，胰岛素似乎对危重症小儿心脏手术患者的骨骼肌降解没有明显影响。
