Abstract
In health, hormones secreted from the gastrointestinal tract have an important role in regulating gastrointestinal motility, glucose metabolism and immune function. Recent studies in the critically ill have established that the secretion of a number of these hormones is abnormal, which probably contributes to disordered gastrointestinal and metabolic function. Furthermore, manipulation of endogenous secretion, physiological replacement and supra-physiological treatment (pharmacological dosing) of these hormones are likely to be novel therapeutic targets in this group. Fasting ghrelin concentrations are reduced in the early phase of critical illness, and exogenous ghrelin is a potential therapy that could be used to accelerate gastric emptying and/or stimulate appetite. Motilin agonists, such as erythromycin, are effective gastrokinetic drugs in the critically ill. Cholecystokinin and peptide YY concentrations are elevated in both the fasting and postprandial states, and are likely to contribute to slow gastric emptying. Accordingly, there is a rationale for the therapeutic use of their antagonists. So-called incretin therapies (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) warrant evaluation in the management of hyperglycaemia in the critically ill. Exogenous glucagon-like peptide-2 (or its analogues) may be a potential therapy because of its intestinotropic properties.
Highlights
In health, peptides released from the stomach and/or intestine modulate motility, secretion, absorption, mucosal growth and immune function of the gastrointestinal tract [1]
Fasting plasma ghrelin concentrations are inversely related to body weight, with relatively lower concentrations in obesity and higher concentrations in anorectic patients [23]
Given its inherent safety profile yet substantial effects on gastrointestinal motility, we studied the effects of exogenous Glucagon-like peptide (GLP)-1 (1.2 pmol/kg/min) in nondiabetic critically ill patients, and established that GLP-1 markedly attenuates the glycaemic response to smallintestinal nutrition (Figure 4) [81]
Summary
Peptides released from the stomach and/or intestine modulate motility, secretion, absorption, mucosal growth and immune function of the gastrointestinal tract [1]. The motor function of the both the proximal and/or distal stomach is disordered in ~50% of critically ill patients and underlies the delayed gastric emptying (which may contribute to a higher frequency, and volume, of gastro-oesophageal reflux events) [6]. The Leuven trial established that marked hyperglycaemia (blood glucose >12 mmol/l) is associated with poor outcomes in surgical intensive care unit patients [15]. This landmark study resulted in a paradigm shift in the management of glycaemia in the critically ill. Safer methods for the management of hyperglycaemia in the critically ill are desirable
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