Feeding intolerance associated poor prognosis of patients with severe neurological conditions

To the editor, We read with great interest the study by JJ Peng et al [1]. The authors found that occurrence of feeding-intolerance (FI) during the early stage of enteral nutrition support in patients with severe neurological conditions, especially elderly stroke patients were associated with a poor prognosis. This study is important and interesting; however, we do still have some concerns about it. Firstly, selection bias cannot be entirely excluded, although it is likely to be minimal as all FI patients during the study period were included and the feed tolerant control group was matched for age, sex, illness severity, some biochemistry indicators, and the occurrence of epilepsy. FI was used as amarker of gastricmotor function, although its relationship with gastric emptying in critically ill patients is unclear. The definition of FI in the literature encompasses a wide range of gastric residue volumes from 75 to 500 ml [2]. However, the cutoff volume of 250ml used in the current study has been used previously in other studies which examined the issue of FI in critical illness. Furthermore, a study by BCHu et al [3] showed that FI within 3 days of NICU admission was not associated with mortality, however, whether FI within 3 days of NICU admission is an independent risk factor for mortality, and whether the results contradict the data of BCHu et al or not, is still unknown in this study. If the conflict occurs, it is presumed that the main reason is due to different subjects in these two studies, the patients in the current study were mainly suffering from severe neurological conditions and the occurrence of FI ismuch earlier. Furthermore, vomiting, abdominal distension, diarrhea, and interruption of enteral nutrition were observed in patients within 3 days of entering NICU in this study, and the possible explanations may be that the function of the brain-gut axis in these patients was damaged, which leads to insufficient gastrointestinal motility and slowed gastrointestinal evacuation [4]. The stress response during the acute phase leads to gastrointestinal ischemia and hypoxia, and it will aggravate gastrointestinal dysfunction and leads to an earlier occurrence of FI. It has been confirmed that FI in critically ill patients is associated with a greater degree of glycemic variation, with a greater number of patients with transient hyperglycemia. These data suggest more intensive insulin therapy may be required to minimize FI, an issue that warrants further study [5]. Additionally, it has been reported that hyperglycemia on presentation was associated with significantly poorer outcomes with stroke patients. We know that cerebral collaterals can partially maintain blood flow to the ischemic penumbra in acute ischemic stroke. We theorized that in ischemic stroke, good collateral circulation may facilitate transport of plasma glucose to the ischemic penumbra, thus worsening glucose neurotoxicity and neurologic outcome, which may not occur in ischemic stroke patients with poor collateral circulation. The greater degree of episodic hyperglycemia in FI patients could potentially reflect greater illness severity [6]. These discrepancies, therefore, cannot be ignored, and the authors should give some interpretation and explanation of these data in the text. Another issue is that the univariate analysis in the current study showed that the APACHE II score was associated with a poor prognosis of patients with severe neurological conditions, but the same result was not found in the multivariate analysis. Actually, other markers of illness severity such as inflammatory cytokines, which impair gastric motility in animals and increase insulin resistance in humans, may be a contributor [7]. Such differences in plasma levels of these cytokines may not be reflected by routine APACHE II scores. On the other hand, the increased blood glucose in FI patients could also be a surrogate of regulatory processes involved in nutrient-induced insulin secretion and other humoral factors such as glucagon-like peptide 1 and amylin, which are known to regulate gastric emptying [8]. The authors should, therefore, perform a detection and analysis of these Inflammatory factors and metabolites in order to achieve optimal results. Finally, as a cohort study, this research can reflect the ‘real-world’ findings and further support the conclusion, but the cohort data may be influenced by bias due to the patient selection process. Therefore, a large-scale study comparing the effectiveness should be conducted in the future.