Description: Prokinetics are drugs that enhance gastrointestinal motility by stimulating the smooth muscle contractions or modulating the neurotransmitters involved in the enteric nervous system(1). Prokinetics can be used to treat various gastrointestinal disorders, such as gastroparesis, gastroesophageal reflux disease, functional dyspepsia, postoperative ileus, and constipation(1). In critically ill patients, prokinetics may improve gastric emptying, enteral feeding tolerance, and prevent complications such as aspiration pneumonia, intra-abdominal hypertension, and abdominal compartment syndrome(2).
Feasibility/Equipment: Prokinetics can be administered orally, intravenously, or subcutaneously, depending on the drug and the patient’s condition(1). Prokinetics require a prescription and should be used with caution in patients with cardiac arrhythmias, electrolyte imbalances, or neuromuscular disorders(1). Prokinetics may interact with other drugs that affect the cytochrome P450 system or prolong the QT interval(1). The dose and frequency of prokinetics may need to be adjusted based on the patient’s renal or hepatic function(1).
Scoring information: The efficacy of prokinetics can be measured by various outcomes, such as gastric residual volume (GRV), gastric emptying time (GET), enteral nutrition delivery, incidence of vomiting or regurgitation, incidence of pneumonia or other infections, intra-abdominal pressure (IAP), organ failure scores, length of stay, and mortality(2,4). The choice of outcome depends on the indication and the goal of prokinetic therapy(2).
Cost: The cost of prokinetics varies depending on the drug, the route of administration, the dose, and the country(1). A systematic review found that prokinetic therapy in critically ill patients was associated with a lower cost per life-year gained compared to no prokinetic therapy(2). However, the cost-effectiveness of prokinetics may depend on the availability and affordability of alternative therapies, such as nasojejunal feeding or surgical decompression(2).
Evidence: There is limited and conflicting evidence on the efficacy and safety of prokinetics in critically ill patients. A meta-analysis of 18 randomized trials found that prokinetics reduced GRV and increased enteral nutrition delivery, but did not reduce pneumonia or mortality(2). Another meta-analysis of 12 randomized trials found that prokinetics improved GET and reduced vomiting, but did not affect GRV or pneumonia(3). A randomized trial of 60 patients with acute pancreatitis and intra-abdominal hypertension found that neostigmine reduced IAP and improved organ function compared to conventional treatment5. However, a randomized trial of 100 patients with feeding intolerance found that itopride did not improve GRV or enteral nutrition delivery compared to metoclopramide(4). More high-quality studies are needed to determine the optimal type, dose, timing, and duration of prokinetic therapy in critically ill patients(2).
Accuracy/Measurement properties: The accuracy and measurement properties of prokinetics depend on the outcome used to assess their efficacy. GRV is a commonly used outcome, but it has low accuracy and reliability as a marker of gastric emptying or feeding intolerance(2). GET is a more accurate outcome, but it requires scintigraphy or breath tests, which are not widely available or feasible in critically ill patients(3). Other outcomes, such as enteral nutrition delivery, pneumonia, IAP, or organ failure scores, may have better validity and reliability, but they are influenced by multiple factors besides prokinetic therapy(2,4).
References:
1: Camilleri M, Atieh J. New Developments in Prokinetic Therapy for Gastric Motility Disorders. Front Pharmacol. 2021 Aug 24;12:711500. doi: 10.3389/fphar.2021.711500.
2: Lewis, K., Alqahtani, Z., Mcintyre, L. et al. The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials. Crit Care 20, 259 (2016). https://doi.org/10.1186/s13054-016-1441-z
3: Elmokadem, E.M., EL Borolossy, R.M., Bassiouny, A.M. et al. The efficacy and safety of itopride in feeding intolerance of critically ill patients receiving enteral nutrition: a randomized, double-blind study. BMC Gastroenterol 21, 126 (2021). https://doi.org/10.1186/s12876-021-01712-w
4: Reintam Blaser, A., Preiser, JC., Fruhwald, S. et al. Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine. Crit Care 24, 224 (2020). https://doi.org/10.1186/s13054-020-02889-4
5: He W, Chen P, Lei Y, Xia L, Liu P, Zhu Y, Zeng H, Wu Y, Ke H, Huang X, Cai W, Sun X, Huang W, Sutton R, Zhu Y, Lu N. Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis. Crit Care. 2022 Mar 3;26(1):52. doi: 10.1186/s13054-022-03922-4.