title: The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials.
abstract: BACKGROUND
  Intolerance to enteral nutrition is common in critically ill adults, and may result in significant morbidity including ileus, abdominal distension, vomiting and potential aspiration events. Prokinetic agents are prescribed to improve gastric emptying. However, the efficacy and safety of these agents in critically ill patients is not well-defined. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy and safety of prokinetic agents in critically ill patients.
  
  
  METHODS
  We searched MEDLINE, EMBASE, and Cochrane Library from inception up to January 2016. Eligible studies included randomized controlled trials (RCTs) of critically ill adults assigned to receive a prokinetic agent or placebo, and that reported relevant clinical outcomes. Two independent reviewers screened potentially eligible articles, selected eligible studies, and abstracted pertinent data. We calculated pooled relative risk (RR) for dichotomous outcomes and mean difference for continuous outcomes, with the corresponding 95 % confidence interval (CI). We assessed risk of bias using Cochrane risk of bias tool, and the quality of evidence using grading of recommendations assessment, development, and evaluation (GRADE) methodology.
  
  
  RESULTS
  Thirteen RCTs (enrolling 1341 patients) met our inclusion criteria. Prokinetic agents significantly reduced feeding intolerance (RR 0.73, 95 % CI 0.55, 0.97; P = 0.03; moderate certainty), which translated to 17.3 % (95 % CI 5, 26.8 %) absolute reduction in feeding intolerance. Prokinetics also reduced the risk of developing high gastric residual volumes (RR 0.69; 95 % CI 0.52, 0.91; P = 0.009; moderate quality) and increased the success of post-pyloric feeding tube placement (RR 1.60, 95 % CI 1.17, 2.21; P = 0.004; moderate quality). There was no significant improvement in the risk of vomiting, diarrhea, intensive care unit (ICU) length of stay or mortality. Prokinetic agents also did not significantly increase the rate of diarrhea.
  
  
  CONCLUSIONS
  There is moderate-quality evidence that prokinetic agents reduce feeding intolerance in critically ill patients compared to placebo or no intervention. However, the impact on other clinical outcomes such as pneumonia, mortality, and ICU length of stay is unclear.
authors.affiliation: Department of Medicine, McMaster University, 1280 Main St West, Hamilton, Ontario, L8S 4L8, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Lewis
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, Ontario, L8S 4L8, Canada.
authors.forename: Zuhoor
authors.initials: Z
authors.lastname: Alqahtani
authors.affiliation: Department of Medicine (Critical Care), The Ottawa Hospital Research Institute, University of Ottawa, 1053 Carling Avenue, Rm F202, Ottawa, Ontario, K1H 8L6, Canada.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: Mcintyre
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, Ontario, L8S 4L8, Canada.|Department of Surgery, McMaster University, 1280 Main St West, Hamilton, Ontario, L8S 4L8, Canada.
authors.forename: Saleh
authors.initials: S
authors.lastname: Almenawer
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 15551, Al-Ain, United Arab Emirates.
authors.forename: Fayez
authors.initials: F
authors.lastname: Alshamsi
authors.affiliation: Department of Intensive Care Medicine, St George's Hospital, Blackshaw Road, London, SW170QT, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rhodes
authors.affiliation: Department of Medicine, Division of Pulmonary Medicine and Critical Care, New York University, 550 First Avenue, New York City, NY, 10016, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Evans
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 4200 Fifth Ave, Pittsburgh, Pennsylvania, 15260, USA.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.affiliation: Department of Medicine, McMaster University, 1280 Main St West, Hamilton, Ontario, L8S 4L8, Canada. alhazzaw@mcmaster.ca.|Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, Ontario, L8S 4L8, Canada. alhazzaw@mcmaster.ca.|Department of Medicine, Division of Critical Care, McMaster University, St Joseph's Healthcare Hamilton, 50 Charlton Avenue, Hamilton, Ontario, L8N 4A6, Canada. alhazzaw@mcmaster.ca.
authors.forename: Waleed
authors.initials: W
authors.lastname: Alhazzani
mesh_terms: D016009:Chi-Square Distribution; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D003967:Diarrhea / Q000517:prevention & control; D004294:Domperidone / Q000494:pharmacology / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D004750:Enteral Nutrition / Q000379:methods / Q000592:standards*; D004917:Erythromycin / Q000494:pharmacology / Q000627:therapeutic use; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration; D007902:Length of Stay / Q000706:statistics & numerical data; D008787:Metoclopramide / Q000494:pharmacology / Q000627:therapeutic use; D012115:Residual Volume / Q000187:drug effects; D014839:Vomiting / Q000517:prevention & control
chemical_list: D018492:Dopamine Antagonists; D004294:Domperidone; D004917:Erythromycin; D008787:Metoclopramide
keywords: Critical illness; Enteral nutrition; Gastroparesis; Prokinetic agents; Systematic review