Pathophysiology and Treatment of Gastrointestinal Motility Disorders in the Acutely Ill

Abstract

Gastrointestinal dysmotility causes delayed gastric emptying, enteral feed intolerance, and functional obstruction of the small and large intestine, the latter functional obstructions being frequently termed ileus and Ogilvie syndrome, respectively. In addition to meticulous supportive care, drug therapy may be appropriate in certain situations. There is, however, considerable variation among individuals regarding what gastric residual volume identifies gastric dysmotility and would encourage use of a promotility drug. While the administration of either metoclopramide or erythromycin is supported by evidence it appears that, dual‐drug therapy (erythromycin and metoclopramide) reduces the rate of treatment failure. There is a lack of evidence to guide drug therapy of ileus, but neither erythromycin nor metoclopramide appear to have a role. Several drugs, including ghrelin agonists, highly selective 5‐hydroxytryptamine receptor agonists, and opiate antagonists are being studied in clinical trials. Neostigmine, when infused at a relatively slow rate in patients receiving continuous hemodynamic monitoring, may alleviate the need for endoscopic decompression in some patients.

Systematic Review With Meta‐Analysis of Patient‐Centered Outcomes, Comparing International Guideline–Recommended Enteral Protein Delivery With Usual Care

“…Recommendations from international critical care guidelines suggest that critically ill patients should receive at least 1.2 g/kg body weight per day of protein via the enteral protein targets, with several studies reporting that during usual critical care management, patients only receive a mean of 0.6-0.8 g/kg per day protein, presumably because of interruptions to feeding, intolerance, and limited availability of higher-protein formulas. [5][6][7][8][9] During critical illness, the frequent occurrence of muscle loss is associated with inferior patient-centered outcomes. 3 Inflammatory mediators, coupled with inactivity, may drive an imbalance between protein breakdown and synthesis, 10,11 with rapid muscle loss of up to 1%-2% of lean body mass per day.…”

Five-fold Gastrointestinal Electrical Stimulation With Electromyography-based Activity Analysis: Towards Multilocular Theranostic Intestinal Implants

“…Diagnosis of motility disorders according to the myoelectric activity and direct electrical stimulation (ES) appears to be reasonable. 7,8 As long-term pharmacological or dietetic treatment may be limited due to side effects and lack of proof of efficacy, 9,10 ES is a promising minimally invasive therapeutic option with potential application in the whole GI tract. However, only a few studies have investigated the effects of multilocular ES in multiple parts of the GI tract in animals or humans.…”

Blinded, Double‐Dummy, Parallel‐Group, Phase 2a Randomized Clinical Trial to Evaluate the Efficacy and Safety of a Highly Selective 5‐Hydroxytryptamine Type 4 Receptor Agonist in Critically Ill Patients With Enteral Feeding Intolerance

“…The treatment of EFI usually involves administration of a prokinetic drug, the most frequently prescribed agent being metoclopramide 4–7 . However, metoclopramide has an adverse event (AE) profile such that there is a need for alternative agents 1,8 …”

“…The nonselective serotonin (5‐hydroxytryptamine) type 4 (5‐HT 4 ) receptor agonist cisapride was previously used as an effective gastrointestinal prokinetic drug to accelerate gastric emptying and reduce EFI in critically ill patients 9–12 . However, cisapride was withdrawn from the market because of the potential for serious cardiovascular events 1 . In contrast to nonselective agonists, highly selective 5‐HT 4 receptor agonists, such as TAK‐954 (previously TD‐8954), appear to have an improved safety profile with respect to the risk of cardiac arrhythmias 13,14 .…”