Structured triglycerides versus physical mixtures of medium- and long-chain triglycerides for parenteral nutrition in surgical or critically ill adult patients: Systematic review and meta-analysis.

INTRODUCTION: New generations of parenteral lipid emulsions combine Long Chain Triglycerides (LCTs) with Medium Chain Triglycerides (MCTs) either by physically mixing MCT- and LCT-containing oils or by using synthetically structured triglycerides (STGs). In order to clarify some open issues relating to their comparative effect, in particular in terms of clinical outcomes, pertinent evidence was systematically identified, reviewed and meta-analyzed. METHODS: PubMed, Scopus, Wanfang Data, China Hospital Knowledge Database and Google Scholar were searched for published clinical trials comparing STGs vs. MCTs/LCTs PN regimens administered over 5-7 days in surgical and/or critically ill patients. Two independent investigators performed screening and data extraction using a predefined list of parameters. Data were pooled using RevMan® 5.2. Quality of evidence was assessed according to Cochrane's risk of bias tool. Pre-specified high quality (HQ), incremental analyses and a post hoc subgroup analysis were performed. RESULTS: 21 studies were included. The meta-analysis revealed a significantly better cumulative nitrogen balance (Std. mean difference [95% CI]) (1.34 [0.98-1.7], p < 0.00001), as well as higher values for pre-albumin (24.99 mg/L [6.71-43.27], p < 0.000001), and albumin (1.22 g/L [0.66-1.77] p < 0.0001), while plasma triglycerides were significantly lower (-0.28 mmol/L [-0.41 to -0.15], p < 0.0001) in the STG vs. MCT/LCT group. ALT, AST, and GGT were significantly lower with STGs than with MCTs/LCTs, while for total bilirubin and ALP only a trend was observed. STGs were also associated with a trend to a shorter hospital length of stay (LOS) (-1.74 days [-3.49 to 0.01] p = 0.05). Quality of evidence was affected by an unclear risk of selection bias, mostly due to the lack of detailed reporting (random sequence generation, allocation concealment). For the other domains, most of the weighted information was judged at low risk of bias. HQ estimated effects, incremental and subgroup analyses were consistent with the main analysis. CONCLUSIONS: In postsurgical and/or critically ill patients, the administration of STGs vs. MCT/LCTs was significantly associated with improved protein economy, better liver tolerance and a more efficient triglyceride elimination. With regard to clinical outcomes a strong trend towards reduced LOS was observed for STG patients.

Does dietary ornithine alpha-ketoglutarate supplementation protect the liver against ischemia-reperfusion injury?

Nutritional supplementation with glutamine, arginine and their precursors has been proposed to contribute to the protection against ischemia-reperfusion-related injuries. The aim of this study was to evaluate in an isolated perfused rat liver model the preventive effect of a 4-day oral ornithine alpha-ketoglutarate (OKG) supplementation against warm ischemia-reperfusion (I-R) injury, and the involvement of nitric oxide synthesis. Rats were fed a controlled regimen supplemented with either OKG (5 g kg(-1); n=15) or an isonitrogenous mixture of non-essential amino acids (Control; n=6) for 4 days. Livers were subsequently prepared for isolated perfusion experiments, including a 45 min no-flow ischemic period. The OKG-treated group was divided into two groups according to the absence (OKG; n=8) or presence of a NO-synthase inhibitor, L-N(omega)-nitro-arginine methyl ester (OKG L-NAME; n=7) during liver perfusion. Liver cytolysis after ischemia was demonstrated by an elevated alanine aminotransferase release during the last 15 min of reperfusion that was significantly higher in the OKG-L-NAME group. Tumor necrosis factor alpha (TNF(alpha)) production was transiently increased only in the control group just after ischemia. At the end of the reperfusion period, liver superoxide dismutase activity was significantly lower in the OKG-L-NAME group compared to control animals. Dietary OKG administration had only a limited effect in this model of mild hepatic I-R, leading mainly to reduced TNF(alpha) production. As the content of lipid peroxidation products was not modified, it seems that OKG acts on the inflammatory response rather than on oxidative reactions. This action can tentatively be attributed to the role of OKG as a glutamine precursor rather than to the synthesis of arginine and nitric oxide.

Protective effects of glutamine dipeptide and alpha-tocopherol against ischemia-reperfusion injury in the isolated rat liver.

BACKGROUND & AIMS: Glutamine and vitamin E may prevent hepatic ischemia-reperfusion (I/R) injuries. Our aim was to investigate the effects of glutamine, either alone or combined with vitamin E, against I/R in the isolated perfused rat liver. METHODS: Four groups of 8 livers from male Sprague-Dawley rats were isolated and submitted to a 45-min no-flow ischemia and reperfusion in the presence of alanine 2 mM, alanine 2 mM plus vitamin E 150 microM, Alanyl-Glutamine (AlaGln) 2 mM, or AlaGln 2 mM plus vitamin E 150 microM. Six non-perfused livers were studied in parallel. Liver function, metabolic parameters, oxidative stress and inflammatory parameters have been studied. RESULTS: AlaGln was rapidly cleared from the perfusate (436+/-41 nmol min(-1) g(-1)) and lowered transaminase release during reperfusion (ALT: -59%), significantly so in the AlaGln+Vit E group (ALT: -65%, p<0.05). The association of glutamine with vitamin E led to lower degrees NO (-83%, p<0.05) production, better preserved hepatic glutathione content and, as with vitamin E alone, preserved hepatic vitamin A and significantly decreased malondialdehyde (-85%, p<0.05). CONCLUSION: Both glutamine, by attenuating inflammatory response, and vitamin E, via its antioxidative properties, showed complementary protective effects against I/R-induced hepatic injury. These data emphasize the potential benefit of combining glutamine and vitamin E supplementation in hepatic I/R injury.

Protective effects of regulatory amino acids on ischemia-reperfusion injury in the isolated perfused rat liver.

OBJECTIVE: Some amino acids (AAs) display potent regulatory activities on cell metabolism, including via anti-oxidative defences. The aim of this study was to evaluate the protective effect of these AAs on warm ischaemia-reperfusion (I/R) injury in the isolated perfused rat liver. MATERIAL AND METHODS: Livers from fasted male Sprague-Dawley rats were isolated and perfused without (control group) or with (AP group) a mixture of regulatory AAs (glutamine, histidine, leucine, methionine, proline, phenylalanine, tryptophan and alanine). After 45 min of perfusion, warm ischaemia was induced for 45 min by clamping the portal vein catheter; thereafter, reperfusion was performed for 30 min. RESULTS: TNF-alpha production was significantly lower in the AP group during reperfusion ( CONTROL: 39+/-7 versus AP: 16+/-2 pg min-1 g-1, p<0.05), and lactate dehydrogenase (LDH) release decreased significantly during the last 15 min of reperfusion ( CONTROL: 0.13+/-0.03 versus AP: 0.04+/-0.02 IU min-1 g-1, p<0.05), despite similar levels of oxidative stress. The addition of regulatory AAs was not associated with variations in portal flow, bile flow, hepatic glucose or urea metabolism. However, significant changes in intrahepatic glutamine ( CONTROL: 1.4+/-0.2 versus AP: 2.6+/-0.5 micromol g-1, p < 0.05) together with higher glutamate release in the AP group ( CONTROL: 10.2+/-5.4 versus AP: 42.6+/-10.9 nmol min-1 g-1, p < 0.05) indicated modifications in nitrogen metabolism. CONCLUSIONS: Taken together, the lower TNF-alpha production, suggesting decreased inflammatory response, the decrease in LDH release in the AP group, demonstrating a better preservation of liver viability, and the increase in hepatic glutamine indicate that AAs play an important role in the liver's response to I/R.