Clinical Division and Laboratory of Intensive Care Medicine, Department Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium.
Intensive Care, Department of Paediatrics and Paediatric Surgery, Erasmus MC, Sophia Children's Hospital, Rotterdam, Netherlands.
Lancet Respir Med. 2017 Jun;5(6):475-483. doi: 10.1016/S2213-2600(17)30186-8. Epub 2017 May 15.
Large randomised controlled trials have shown that early supplemental parenteral nutrition in patients admitted to adult and paediatric intensive care units (PICUs) is harmful. Overdosing of energy with too little protein was suggested as a potential reason for this. This study analysed which macronutrient was associated with harm caused by early supplemental parenteral nutrition in the Paediatric Early versus Late Parenteral Nutrition In Critical Illness (PEPaNIC) randomised trial.
Patients in the initial randomised controlled trial were randomly assigned to receive suppplemental parenteral nutrition (PN) within 24 h of PICU admission (early PN) or to receive such PN after 1 week (late PN) when enteral nutrition was insufficient. In this post-randomisation, observational study, doses of glucose, lipids, and aminoacids administered during the first 7 days of PICU stay were expressed as % of reference doses from published clinical guidelines for age and weight. Independent associations between average macronutrient doses up to each of the first 7 days and likelihood of acquiring an infection in the PICU, of earlier live weaning from mechanical ventilation, and of earlier live PICU discharge were investigated using multivariable Cox proportional hazard analyses. The three macronutrients were included in the analysis simultaneously and baseline risk factors were adjusted for.
From June 18, 2012, to July 27, 2015, 7519 children aged between newborn and 17 years were assessed for eligibility. 6079 patients were excluded, and 1440 children were randomly assigned to receive either early PN (n=723) or late PN (n=717). With increasing doses of aminoacids, the likelihood of acquiring a new infection was higher (adjusted hazard ratios [HRs] per 10% increase between 1·043-1·134 for days 1-5, p≤0·029), while the likelihood of earlier live weaning from mechanical ventilation was lower (HRs 0·950-0·975 days 3-7, p≤0·045), and the likelihood of earlier live PICU discharge was lower (HRs 0·943-0·972 days 1-7, p≤0·030). By contrast, more glucose during the first 3 days of PICU stay was independently associated with fewer infections (HRs 0·870-0·913, p≤0·036), whereas more lipids was independently associated with earlier PICU discharge (HRs 1·027-1·050, p≤0·043 days 4-7). Risk of harm with aminoacids was also shown for low doses.
These associations suggest that early administration of aminoacids, but not glucose or lipids, could explain harm caused by early supplemental parenteral nutrition in critically ill children.
Flemish Agency for Innovation through Science and Technology; UZLeuven Clinical Research Fund; Research Foundation Flanders; Methusalem Programme Flemish Government; European Research Council; Fonds-NutsOhra; Erasmus-MC Research Grant; Erasmus Trustfonds.
大型随机对照试验表明，在成人和儿科重症监护病房（PICU）入院的患者中早期补充肠外营养是有害的。过量的能量与蛋白质不足被认为是潜在的原因。本研究分析了在儿科早期与晚期肠外营养在危重病中的随机试验（PEPaNIC）中，哪种宏量营养素与早期补充肠外营养引起的危害有关。
最初的随机对照试验中的患者被随机分配在 PICU 入院后 24 小时内（早期 PN）或在肠内营养不足时接受补充肠外营养（PN）（晚期 PN）。在这项事后随机、观察性研究中，在 PICU 住院的前 7 天内给予的葡萄糖、脂肪和氨基酸剂量表示为发表的临床指南中年龄和体重的参考剂量的%。使用多变量 Cox 比例风险分析研究在 PICU 住院期间的前 7 天内每天平均宏量营养素剂量与感染的可能性、机械通气的早期撤机和早期 PICU 出院之间的独立关联。同时分析了三种宏量营养素，并调整了基线风险因素。
从 2012 年 6 月 18 日至 2015 年 7 月 27 日，评估了 7519 名年龄在新生儿至 17 岁之间的儿童的资格。排除了 6079 名患者，1440 名儿童被随机分配接受早期 PN（n=723）或晚期 PN（n=717）。随着氨基酸剂量的增加，感染的可能性更高（第 1-5 天每增加 10%的调整后的危险比[HRs]为 1.043-1.134，p≤0.029），而机械通气的早期撤机可能性较低（HRs 第 3-7 天为 0.950-0.975，p≤0.045），早期 PICU 出院的可能性也较低（HRs 第 1-7 天为 0.943-0.972，p≤0.030）。相比之下，在 PICU 住院的前 3 天内给予更多的葡萄糖与感染减少独立相关（HRs 为 0.870-0.913，p≤0.036），而给予更多的脂肪与更早的 PICU 出院独立相关（HRs 为 1.027-1.050，p≤0.043 天 4-7）。低剂量的氨基酸也显示出对危害的风险。
这些关联表明，早期给予氨基酸可能会导致危重症儿童早期补充肠外营养引起的危害，而不是葡萄糖或脂肪。
佛兰德创新科学与技术局；鲁汶大学临床研究基金；佛兰德研究基金会；佛兰德政府梅索米努斯计划；欧洲研究理事会；Methusalem 计划佛兰德政府；Erasmus-MC 研究赠款；Erasmus 信托基金。
