早期肠外营养不会恶化肠屏障功能：初步随机对照研究

　　多项回顾性研究发现，在重症儿童患者中，肠外营养（PN）与死亡率显著相关，其可能的机制包括肠屏障功能障碍和肠道微生物多样性减少。

　　为了明确早期PN联合肠内营养（EN）对重症儿童患者肠道功能的影响，亚利桑那大学、新墨西哥大学入组10例急性呼吸窘迫综合征（ARDS）儿童患者进行随机对照研究，两组患者分别在EN的基础上给予早期（第1天）或晚期（第5天）联合PN，监测血浆FABP2、密封蛋白-3和瓜氨酸水平，发现早期PN联合EN并不导致肠黏膜屏障功能受损，并提示早期EN能预防PN相关的肠屏障功能障碍。

JPEN J Parenter Enteral Nutr. 2016;40(4):121.

Early Parenteral Nutrition Does Not Worsen Intestinal Barrier Function: A Pilot RCT.

Katri Typpo; Claire Larmonier; Jendar Deschenes; Daniel Laubitz; Christy Harrison; Kareem W. Shehab; Pawel Kiela; Fayez Ghishan.

University of Arizona, Tucson, AZ, USA; University of New Mexico, Albuquerque, NM, USA.

Purpose: Multiple retrospective studies associate parenteral nutrition (PN) with mortality in critically children. Putative mechanisms for this increased mortality are via intestinal barrier dysfunction and/or loss of intestinal microbiome diversity when PN is provided in the absence of enteral nutrition (EN). We sought to understand if early PN provided with EN worsens intestinal barrier function and microbiome diversity during pediatric critical illness.

Methods: Single-center pilot RCT of early (day 1) vs late PN (day 5) to supplement early EN, for children admitted to Diamond Children's Medical Center, Tucson, AZ, with acute respiratory distress syndrome (ARDS) from August 2012 to December 2014. Block randomization was stratified by age and body mass index z score to early or standard care PN. All patients had early EN initiated and advanced according to our standard early EN guideline. For patients in the early PN arm, PN began within 4 hours of randomization and was titrated to deliver 100%-120% of measured resting energy expenditure in combination with advancing EN. We examined repeated plasma biomarkers at baseline and throughout the first 7 days of pediatric intensive care unit hospitalization to reflect intestinal barrier function (FABP2, epithelial integrity; citrulline, functional enterocyte mass; claudin 3, tight junction integrity). We examined fecal microbiome composition and diversity daily during the 1-week study period in 2 twin-study patients. DNA was purified with phenol-chloroform protocol with bead beating. Microbiota taxonomic analysis was performed by sequencing V4 fragment of 16S rRNA gene on MiSeq Illumina, followed by bioinformatic analysis with MacQiime (v. 1.9.1).

Results: We enrolled 10 study subjects in this pilot RCT. Median age was 2.0 years (range, 0.12-13.6 years). Patients had elevated baseline FABP2 (median, 467 pg/mL; IQR, 387-1151 pg/mL) and below-normal citrulline (median, 7.1 μmol/L; IQR, 4.6-10 μmol/L) concentrations at time of randomization, indicative of poor intestinal epithelial integrity and low functional enterocyte mass, respectively. Patients in the early PN arm had a nonsignificant trend for improved FABP2 concentrations (P > 0.05). Patients exposed to early PN did not have a trend for worse claudin 3 or citrulline concentrations. Exposure to PN was associated with predominance of Clostridiales (67-73.4%) rather than Bifidobacteriales (47.7%-65.6%) on days 1-2 of the study protocol. Lactobacillales had low abundance (1.4%-5.5%) in both patients on study days 1-2 but increased abundance (87%-99.6%) on days 3-7. Weighted UniFrac differences for β diversity demonstrated differences between patients on study days 1-2 but not on study days 3-7. Both patients were treated with intravenous antimicrobials throughout the 7-day study period.

Conclusions: Patients randomized to early PN as a supplement to EN in this pilot RCT did not demonstrate worsened intestinal barrier function. Trends in our data indicate that early EN may prevent PN-associated loss of intestinal barrier function in children with ARDS. Exposure to antimicrobials may dominate PN effects on intestinal microbial population diversity. Further studies are needed to understand if early PN might improve intestinal barrier function for children with ARDS and which aspects of intensive care unit care most alter intestinal microbiome composition and diversity.

Financial support: National Institutes of Health, Eunice Kennedy Shriver National Institute for Child Health and Human Development.