Impact of withholding early parenteral nutrition in adult critically ill patients on ketogenesis in relation to outcome

Bruyn, Astrid De; Langouche, Lies; Perre, Sarah Vander; Gunst, Jan; Berghe, Greet Van den

doi:10.1186/s13054-021-03519-3

Cited by 12 publications

(15 citation statements)

References 5 publications

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“…In contrast, the (modest) rise in ketones found in the adult study did not independently associate with the outcome benefit of withholding PN [31]. Moreover, both in the children as well as in the adults, the ketogenic response was not associated with the decreased incidence of nosocomial infections due to withholding PN [7,31]. This could indicate other mediating mechanisms exerted during the fasting response parallel to ketogenesis, such as autophagy.…”

Section: Considerations For the Implementation Of Intermittent Fasting In Critically Ill Childrencontrasting

confidence: 56%

“…Interestingly, the increased ketogenesis in critically ill children statistically mediated part of the beneficial impact of withholding parenteral nutrition on weaning from respiratory support and on time to live PICU discharge [7]. In contrast, the (modest) rise in ketones found in the adult study did not independently associate with the outcome benefit of withholding PN [31]. Moreover, both in the children as well as in the adults, the ketogenic response was not associated with the decreased incidence of nosocomial infections due to withholding PN [7,31].…”

Section: Considerations For the Implementation Of Intermittent Fasting In Critically Ill Childrenmentioning

confidence: 81%

“…A significant ketogenesis was already observed 0e7 h (median 36 min [IQR 18e74]) after admission in critically ill children in the PEPaNIC RCT [7]. A similar secondary analysis of the adult EPaNIC RCT, investigating withholding PN in critically ill adults, showed that ketone levels were only modestly elevated, as compared with the paediatric population [31]. This indicates that aside from the nutritional intake and/or status prior to PICU admission, ketogenesis during critical illness also depends on age.…”

Section: Considerations For the Implementation Of Intermittent Fasting In Critically Ill Childrenmentioning

confidence: 86%

“…This novel strategy, in which low macronutrient intakes were accepted during the first week of PICU, improved short-as well as long-term outcome of critically ill children, independent of age or nutritional status [24,26e29]. These counterintuitive findings, corroborating those from adult ICU studies [30], were attributed to a 'fasting response', characterized by increased ketogenesis and endocrine response [7,24,30,31]. The low nutritional intake and the response heron resembled 'caloric restriction' strategies, which have consistently shown to have clear disease-modifying abilities in animal and human studies on a wide range of diseases [32e48].…”

Section: Current Evidence For Intermittent Versus Continuous Nutrition In the Paediatric Intensive Care Unitmentioning

confidence: 93%

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Intermittent fasting in paediatric critical illness: The properties and potential beneficial effects of an overnight fast in the PICU

et al. 2021

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Although evidence for the superiority of continuous feeding over intermittent feeding is lacking, in most paediatric intensive care units (PICU) artificial feeding is administered continuously for 24 h per day. Until now, studies in PICU on intermittent feeding have primarily focused on surrogate endpoints such as nutritional intake and gastro-intestinal complaints and none have studied the effects of an extended fasting period. Intermittent fasting has been proven to have many health benefits in both animal and human studies. The observed beneficial effects are based on multiple metabolic and endocrine changes that are presumed crucial in critical illness as well. One key element is the transition to ketone body metabolism, which, among others, contributes to the stimulation of several cellular pathways involved in stress resistance (neuro)plasticity and mitochondrial biogenesis, and might help preserve brain function. Secondly, the fasting state stimulates the activation of autophagy, a process that is crucial for cellular function and integrity. Of the different intermittent fasting strategies investigated, time-restricted feeding with a daily extended fasting period appears most feasible in the PICU. Moreover, planning the fasting period overnight could help maintain the circadian rhythm. Although not investigated, such an overnight intermittent fasting strategy might improve the metabolic profile, feeding tolerance and perhaps even have beneficial effects on tissue repair, reperfusion injury, muscle weakness, and the immune response. Future studies should investigate practical implications in critically ill children and the optimal duration of the fasting periods, which might be affected by the severity of illness and by age.

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Section: Considerations For the Implementation Of Intermittent Fasting In Critically Ill Childrencontrasting

confidence: 56%

Section: Considerations For the Implementation Of Intermittent Fasting In Critically Ill Childrenmentioning

confidence: 81%

Section: Considerations For the Implementation Of Intermittent Fasting In Critically Ill Childrenmentioning

confidence: 86%

Section: Current Evidence For Intermittent Versus Continuous Nutrition In the Paediatric Intensive Care Unitmentioning

confidence: 93%

See 2 more Smart Citations

Intermittent fasting in paediatric critical illness: The properties and potential beneficial effects of an overnight fast in the PICU

et al. 2021

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“…Although ketogenesis has traditionally been reported to be blunted in critical illness [ 5 – 7 ], a recent pilot crossover RCT revealed that four hours of full fasting significantly increased blood ketone concentrations in long-stay critically ill patients [ 8 ]. Moreover, we recently demonstrated that withholding parenteral nutrition during the first week of intensive care unit (ICU) stay and hereby temporarily accepting insufficient enteral nutrition, significantly increased ketogenesis in critically ill children and adults [ 9 , 10 ]. Activation of ketogenesis by such virtual fasting early during critical illness was most pronounced in children, in whom increased ketone availability also statistically mediated part of the outcome benefit of the intervention [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

et al. 2021

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Background Recent evidence suggests a potentially protective effect of increasing ketone body availability via accepting low macronutrient intake early after onset of critical illness. The impact of blood glucose control with insulin on circulating ketones is unclear. Whereas lowering blood glucose may activate ketogenesis, high insulin concentrations may have the opposite effect. We hypothesized that the previously reported protective effects of tight glucose control in critically ill patients receiving early parenteral nutrition may have been mediated in part by activation of ketogenesis. Methods This is a secondary analysis of 3 randomized controlled trials on tight versus liberal blood glucose control in the intensive care unit, including 700 critically ill children and 2748 critically ill adults. All patients received early parenteral nutrition as part of the contemporary standard of care. Before studying a potential mediator role of circulating ketones in improving outcome, we performed a time course analysis to investigate whether tight glucose control significantly affected ketogenesis and to identify a day of maximal effect, if any. We quantified plasma/serum 3-hydroxybutyrate concentrations from intensive care unit admission until day 3 in 2 matched subsets of 100 critically ill children and 100 critically ill adults. Univariable differences between groups were investigated by Kruskal-Wallis test. Differences in 3-hydroxybutyrate concentrations between study days were investigated by Wilcoxon signed-rank test. Results In critically ill children and adults receiving early parenteral nutrition, tight glucose control, as compared with liberal glucose control, lowered mean morning blood glucose on days 1–3 (P < 0.0001) via infusing insulin at a higher dose (P < 0.0001). Throughout the study period, caloric intake was not different between groups. In both children and adults, tight glucose control did not affect 3-hydroxybutyrate concentrations, which were suppressed on ICU days 1–3 and significantly lower than the ICU admission values for both groups (P < 0.0001). Conclusion Tight versus liberal glucose control in the context of early parenteral nutrition did not affect 3-hydroxybutyrate concentrations in critically ill patients. Hence, the protective effects of tight glucose control in this context cannot be attributed to increased ketone body availability.

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Nutrition in the intensive care unit: from the acute phase to beyond

de Man,

Gunst,

Reintam Blaser

2024

Intensive Care Med

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Impact of withholding early parenteral nutrition in adult critically ill patients on ketogenesis in relation to outcome

Cited by 12 publications

References 5 publications

Intermittent fasting in paediatric critical illness: The properties and potential beneficial effects of an overnight fast in the PICU

Intermittent fasting in paediatric critical illness: The properties and potential beneficial effects of an overnight fast in the PICU

Impact of tight glucose control on circulating 3-hydroxybutyrate in critically ill patients

Nutrition in the intensive care unit: from the acute phase to beyond

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