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Delayed gastric emptying occurs in critically ill patients and impairs the delivery, digestion, and absorption of enteral feeding. A pathophysiologic role of the enterohormones peptide YY and ghrelin is supported by preclinical data. To compare the circulating plasma levels of peptide YY and ghrelin in control subjects and in critically ill patients, during feeding and fasting, and to search for a correlation with gastric emptying.A prospective observational trial.Mixed ICU of an academic hospital.Healthy volunteers and patients expected to stay in ICU for at least 3 days in whom enteral nutrition was indicated.None.Plasma peptide YY and ghrelin (enzyme-linked immunosorbent assay) were measured once in 10 fasting volunteers (controls) and daily from admission until day 5 of the ICU stay in 30 critically ill patients (median [interquartile range] age 63 [57–67] yr, median [interquartile range] Acute Physiology and Chronic Health Evaluation II score 21 [14–24]). Eight patients could not be fed (fasting group). In fed patients, 13 never had a gastric residual volume higher than 250 mL (low gastric residual volume group), in contrast to the high gastric residual volume group (n = 9). The plasma levels of peptide YY did not differ between patients (6.4 [0–18.1] pg/mL) and controls (4.8 [0.3–17.7] pg/mL). Ghrelin levels were lower in patients than in control (213 [54.4–522.7] vs 1,435 [1,321.9–1,869.3] pg/mL; p < 0.05). Plasma peptide YY or ghrelin did not differ between fasting and fed patients or between the high and low gastric residual volume groups.In critically ill patients, plasma concentration of ghrelin significantly differs from that of controls, irrespective of the feeding status. No correlation was found between the temporal profile of ghrelin or peptide YY plasma concentration with bedside functional assessment of gastric emptying.