Advertisement

In Search of the Ideal Promotility Agent: Optimal Use of Currently Available Promotility Agents for Nutrition Therapy of the Critically Ill Patient

  • Sarah J. DiamondEmail author
  • Endashaw Omer
  • Laszlo Kiraly
Nutrition and Obesity (S McClave and J Obert, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Nutrition and Obesity

Abstract

Purpose of Review

Enteral nutrition therapy is essential in the management of critically ill patients. Prokinetic agents have been used successfully to aid in the delivery of nutrition and improve feeding tolerance in patients in the intensive care unit (ICU). The aim of this report is to review the existing promotility agents available for use in the critically ill as well as outline the role of potential investigative drugs in order to provide a guide to the management of this difficult and important clinical dilemma.

Recent Findings

While no single currently available agent currently meets all of the desired goals in the critical care setting, there are an increasing number of available agents from which to choose including motilin receptor agonists, 5HT4 receptor agonists, D2 receptor antagonists, and Mu opioid receptor antagonists.

Summary

We recommend a multifaceted approach to optimizing enteral nutrition in the critical care setting which should include the early, prophylactic use of promotility agents and should focus on the management of reversible causes of impaired gastrointestinal motility.

Keywords

Gastrointestinal dysmotility Prokinetics Promotility Early enteral nutrition 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    McClave SA, Martindale RG, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2009;33(3):277–316.CrossRefPubMedGoogle Scholar
  2. 2.
    Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian critical care clinical practice guidelines committee. Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003;27(5):355–73.CrossRefPubMedGoogle Scholar
  3. 3.
    Ritz MA, Fraser R, Tam W, Dent J. Impacts and patterns of disturbed gastrointestinal function in critically ill patients. Am J Gastroenterol. 2000;95(11):3044–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Madl C, Druml W. Gastrointestinal disorders of the critically ill. Systemic consequences of ileus. Best Pract Res Clin Gastroenterol. 2003;17(3):445–56.CrossRefPubMedGoogle Scholar
  5. 5.
    •• Stupak DP, Abdelsayed GG, Soloway GN. Motility disorders of the upper gastrointestinal tract in the intensive care unit: pathophysiology and contemporary management. J Clin Gastroenterol. 2012;46(6):449–56. This review article outlines the pathophysiology and clinical presentation of upper gastrointestinal motility disturbances in the intensive care unit. CrossRefPubMedGoogle Scholar
  6. 6.
    Overhaus M, Togel S, Pezzone MA, Bauer AJ. Mechanisms of polymicrobial sepsis-induced ileus. Am J Physiol Gastrointest Liver Physiol. 2004;287(3):G685–94.CrossRefPubMedGoogle Scholar
  7. 7.
    Nguyen NQ, Ng MP, Chapman M, Fraser RJ, Holloway RH. The impact of admission diagnosis on gastric emptying in critically ill patients. Crit Care. 2007;11(1):R16.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nguyen NQ, Chapman MJ, Fraser RJ, et al. The effects of sedation on gastric emptying and intra-gastric meal distribution in critical illness. Intensive Care Med. 2008;34(3):454–60.CrossRefPubMedGoogle Scholar
  9. 9.
    Bouras EP, Vazquez Roque MI, Aranda-Michel J. Gastroparesis: from concepts to management. Nutr Clin Pract. 2013;28(4):437–47.CrossRefPubMedGoogle Scholar
  10. 10.
    Rice TW. Gastric residual volume: end of an era. JAMA. 2013;309(3):283–4.CrossRefPubMedGoogle Scholar
  11. 11.
    Elke G, Felbinger TW, Heyland DK. Gastric residual volume in critically ill patients: a dead marker or still alive? Nutr Clin Pract. 2015;30(1):59–71.CrossRefPubMedGoogle Scholar
  12. 12.
    Kao CH, ChangLai SP, Chieng PU, Yen TC. Gastric emptying in head-injured patients. Am J Gastroenterol. 1998;93(7):1108–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Tarling MM, Toner CC, Withington PS, Baxter MK, Whelpton R, Goldhill DRA. Model of gastric emptying using paracetamol absorption in intensive care patients. Intensive Care Med. 1997;23(3):256–60.CrossRefPubMedGoogle Scholar
  14. 14.
    Elke G, Heyland D. Residual gastric volume and risk of ventilator-associated pneumonia. JAMA. 2013;309(20):2090.CrossRefPubMedGoogle Scholar
  15. 15.
    • Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. American College of Gastroenterology. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18–37. quiz 38. These guidelines offer an evidence-based approach to the management of delayed gastric emptying which can be applied to critically ill patients. CrossRefPubMedGoogle Scholar
  16. 16.
    Poulard F, Dimet J, Martin-Lefevre L, et al. Impact of not measuring residual gastric volume in mechanically ventilated patients receiving early enteral feeding: a prospective before-after study. JPEN J Parenter Enteral Nutr. 2010;34(2):125–30.CrossRefPubMedGoogle Scholar
  17. 17.
    Reignier J, Mercier E, Le Gouge A, et al. Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA. 2013;309(3):249–56.CrossRefPubMedGoogle Scholar
  18. 18.
    Dive A, Moulart M, Jonard P, Jamart J, Mahieu P. Gastroduodenal motility in mechanically ventilated critically ill patients: a manometric study. Crit Care Med. 1994;22(3):441–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Caddell KA, Martindale R, McClave SA, Miller K. Can the intestinal dysmotility of critical illness be differentiated from postoperative ileus? Curr Gastroenterol Rep. 2011;13(4):358–67.CrossRefPubMedGoogle Scholar
  20. 20.
    McClave SA, Sexton LK, Spain DA, et al. Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. Crit Care Med. 1999;27(7):1252–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Herbert MK, Holzer P. Standardized concept for the treatment of gastrointestinal dysmotility in critically ill patients—current status and future options. Clin Nutr. 2008;27(1):25–41.CrossRefPubMedGoogle Scholar
  22. 22.
    Pinilla JC, Samphire J, Arnold C, Liu L, Thiessen B. Comparison of gastrointestinal tolerance to two enteral feeding protocols in critically ill patients: a prospective, randomized controlled trial. JPEN J Parenter Enteral Nutr. 2001;25(2):81–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Heyland DK, Murch L, Cahill N, et al. Enhanced protein-energy provision via the enteral route feeding protocol in critically ill patients: results of a cluster randomized trial. Crit Care Med. 2013;41(12):2743–53.CrossRefPubMedGoogle Scholar
  24. 24.
    Itoh Z, Suzuki T, Nakaya M, Inoue M, Mitsuhashi S. Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut. Antimicrob Agents Chemother. 1984;26(6):863–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Itoh Z, Nakaya M, Suzuki T, Arai H, Wakabayashi K. Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Phys. 1984;247(6 Pt 1):G688–94.Google Scholar
  26. 26.
    Janssens J, Peeters TL, Vantrappen G, et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med. 1990;322(15):1028–31.CrossRefPubMedGoogle Scholar
  27. 27.
    Chapman MJ, Fraser RJ, Kluger MT, Buist MD, De Nichilo DJ. Erythromycin improves gastric emptying in critically ill patients intolerant of nasogastric feeding. Crit Care Med. 2000;28(7):2334–7.CrossRefPubMedGoogle Scholar
  28. 28.
    MacLaren R, Kiser TH, Fish DN, Wischmeyer PE. Erythromycin vs metoclopramide for facilitating gastric emptying and tolerance to intragastric nutrition in critically ill patients. JPEN J Parenter Enteral Nutr. 2008;32(4):412–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Depoortere I, Peeters TL, Vantrappen G. Development of motilin receptors and of motilin- and erythromycin-induced contractility in rabbits. Gastroenterology. 1990;99(3):652–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Potter TG, Snider KR. Azithromycin for the treatment of gastroparesis. Ann Pharmacother. 2013;47(3):411–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Chini P, Toskes PP, Waseem S, Hou W, McDonald R, Moshiree B. Effect of azithromycin on small bowel motility in patients with gastrointestinal dysmotility. Scand J Gastroenterol. 2012;47(4):422–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Enweluzo C, Aziz F. Gastroparesis: a review of current and emerging treatment options. Clin Exp Gastroenterol. 2013;6:161–5.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Camilleri M, Acosta A. Emerging treatments in neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist. Neurogastroenterol Motil. 2015;27(3):324–32.CrossRefPubMedGoogle Scholar
  34. 34.
    Barshop K, Kuo B. The investigational drug camicinal for the treatment of gastroparesis. Expert Opin Investig Drugs. 2015;24(1):133–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Fraser RJ, Bryant L. Current and future therapeutic prokinetic therapy to improve enteral feed intolerance in the ICU patient. Nutr Clin Pract. 2010;25(1):26–31.CrossRefPubMedGoogle Scholar
  36. 36.
    Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug insight: from disturbed motility to disordered movement—a review of the clinical benefits and medicolegal risks of metoclopramide. Nat Clin Pract Gastroenterol Hepatol. 2006;3(3):138–48.CrossRefPubMedGoogle Scholar
  37. 37.
    Ehrenpreis ED, Deepak P, Sifuentes H, Devi R, Du H, Leikin JB. The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits. Am J Gastroenterol. 2013;108(6):866–72.CrossRefPubMedGoogle Scholar
  38. 38.
    Kessing BF, Smout AJ, Bennink RJ, Kraaijpoel N, Oors JM, Bredenoord AJ. Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects. Neurogastroenterol Motil. 2014;26(8):1079–86.CrossRefPubMedGoogle Scholar
  39. 39.
    Aderinto-Adike AO, Quigley EM. Gastrointestinal motility problems in critical care: a clinical perspective. J Dig Dis. 2014;15(7):335–44.CrossRefGoogle Scholar
  40. 40.
    Patterson D, Abell T, Rothstein R, Koch K, Barnett JA. Double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Am J Gastroenterol. 1999;94(5):1230–4.PubMedGoogle Scholar
  41. 41.
    Rohm KD, Boldt J, Piper SN. Motility disorders in the ICU: recent therapeutic options and clinical practice. Curr Opin Clin Nutr Metab Care. 2009;12(2):161–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Bragg D, El-Sharkawy AM, Psaltis E, Maxwell-Armstrong CA, Lobo DN. Postoperative ileus: recent developments in pathophysiology and management. Clin Nutr. 2015;34(3):367–76.CrossRefPubMedGoogle Scholar
  43. 43.
    Moss J, Rosow CE. Development of peripheral opioid antagonists’ new insights into opioid effects. Mayo Clin Proc. 2008;83(10):1116–30.CrossRefPubMedGoogle Scholar
  44. 44.
    Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med. 2008;358(22):2332–43.CrossRefPubMedGoogle Scholar
  45. 45.
    Pfab F, Nowak-Machen M, Napadow V, Fleckenstein J. Alternatives to prokinetics to move the pylorus and colon. Curr Opin Clin Nutr Metab Care. 2012;15(2):166–73.CrossRefPubMedGoogle Scholar
  46. 46.
    Sawh SB, Selvaraj IP, Danga A, Cotton AL, Moss J, Patel PB. Use of methylnaltrexone for the treatment of opioid-induced constipation in critical care patients. Mayo Clin Proc. 2012;87(3):255–9.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Tan EK, Cornish J, Darzi AW, Tekkis PP. Meta-analysis: alvimopan vs. placebo in the treatment of post-operative ileus. Aliment Pharmacol Ther. 2007;25(1):47–57.PubMedGoogle Scholar
  48. 48.
    Leppert W. Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction. Drug Des Devel Ther. 2015;9:2215–31.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Busby RW, Kessler MM, Bartolini WP, et al. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther. 2013;344(1):196–206.CrossRefPubMedGoogle Scholar
  50. 50.
    Lee YY. What’s new in the toolbox for constipation and fecal incontinence? Front Med (Lausanne). 2014;1:5.Google Scholar
  51. 51.
    Zeinali F, Stulberg JJ, Delaney CP. Pharmacological management of postoperative ileus. Can J Surg. 2009;52(2):153–7.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Valle RG, Godoy FL. Neostigmine for acute colonic pseudo-obstruction: a meta-analysis. Ann Med Surg (Lond). 2014;3(3):60–4.CrossRefGoogle Scholar
  53. 53.
    Nguyen NQ, Fraser RJ, Chapman MJ, et al. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Crit Care Med. 2007;35(1):82–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Pfab F, Winhard M, Nowak-Machen M, et al. Acupuncture in critically ill patients improves delayed gastric emptying: a randomized controlled trial. Anesth Analg. 2011;112(1):150–5.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sarah J. Diamond
    • 1
    Email author
  • Endashaw Omer
    • 2
  • Laszlo Kiraly
    • 3
  1. 1.Division of Gastroenterology and HepatologyOregon Health and Science UniversityPortlandUSA
  2. 2.Division of Gastroenterology and HepatologyUniversity of LouisvilleLouisvilleUSA
  3. 3.Department of SurgeryOregon Health and Science UniversityPortlandUSA

Personalised recommendations