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Intravenous amino acid supplementation reduces 28-d mortality in sepsis: a retrospective cohort study from Medical Information Mart for Intensive Care-IV database and Mendelian randomisation analysis
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DOI：10.1017/S0007114526106461.png)
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Abstract
En 中文
Sepsis-related deaths remain prevalent in intensive care settings; with metabolic dysregulation as a key contributor. Although amino acid supplementation has shown promise; its clinical effectiveness in sepsis is unclear. This study evaluated the impact of intravenous amino acid administration on 28-d mortality in intensive care unit (ICU) sepsis patients using retrospective cohort analysis and Mendelian randomisation (MR). We analysed data from the Medical Information Mart for Intensive Care-IV database; matching 726 patients (363 per group) using propensity scores. The association between amino acid supplementation and mortality was assessed using logistic regression; Cox regression and targeted maximum likelihood estimation (TMLE). Two-sample MR was used to explore causal links between twenty common amino acids and sepsis mortality. In the cohort analysis; amino acid supplementation was consistently associated with significantly reduced 28-d mortality across all analytical methods (logistic regression: OR = 0·48; P < 0·01; Cox regression: HR = 0·48; P < 0·01; TMLE: average treatment effect = −0·102; P < 0·01). In contrast; the MR analysis did not find a significant causal association for any single amino acid after correction for multiple comparisons; although glycine showed a nominal protective signal; it did not remain significant after false discovery rate correction. This dual-method study demonstrates a strong association between compound amino acid infusions and reduced mortality in sepsis but did not identify any single amino acid as a robust causal mediator. These findings suggest the benefit may arise from a synergistic effect; highlighting the need for randomised controlled trials to validate these observational results and optimise nutritional strategies.
Keywords:
Sepsis
Amino acids
Mortality
Mendelian randomisation
Propensity score matching
false discovery rate
intensive care unit
mean arterial pressure
Medical Information Mart for Intensive Care-IV
Mendelian randomisation
propensity score matching
single nucleotide polymorphism
targeted maximum likelihood estimation
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3
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