The Efficacy and Safety of Prokinetic Agents in Critically ill Patients Receiving Enteral Nutrition: A Systematic Review and Meta-analysis of Randomized Trials
CCCF ePoster library. Lewis K. 11/02/16; 151004; 122 Disclosure(s)(s): no
Dr. Kim Lewis
Dr. Kim Lewis
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Topic: Systematic Review, Meta-analysis, or Meta-synthesis

The Efficacy and Safety of Prokinetic Agents in Critically ill Patients Receiving Enteral Nutrition: A Systematic Review and Meta-analysis of Randomized Trials

Lewis, Kimberley1; Alqahtani, Zuhoor2; Waleed Alhazzani1,2
Department of Medicine, McMaster University, Hamilton, Canada; 2 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada


Introduction: Impaired tolerance to enteral nutrition is common in critically ill adults (1) as a result of many factors such as medications, hyperglycemia or the disease process itself (2-6). Untreated slow gastric emptying can cause vomiting, aspiration, pneumonia, and inadequate provision of calories (7-12). Despite these risks, enteral feeding is preferred to parenteral nutrition as it is associated with fewer septic complications, decreased bacterial translocation and is cheaper (13-20). Prokinetic agents may improve gastric emptying and reduce the risk of feeding intolerance. The most recent systematic review in this important area was published more than a decade ago (21). Since that time, multiple randomized trails have been published (22-26) and Cisapride has been withdrawn from market (27-30).
Objectives: We aim to conduct a systematic review and meta-analysis to determine the efficacy of prokinetic agents in critically ill adults.
Methods: We searched MEDLINE, EMBASE, and Cochrane Library. Eligible studies included randomized control trials (RCTs) of critically ill adults admitted to the intensive care unit (ICU) who received metoclopramide, domperidone or erythromycin and reported clinically significant outcomes such as vomiting, aspiration, mortality, length of stay (LOS), diarrhea, post-pyloric feeding tube placement and feeding intolerance. Two independent reviewers screened potentially eligible articles, selected eligible studies, and abstracted data. We calculated pooled relative risk (RR) for dichotomous outcomes and mean differences for continuous outcomes, with the corresponding 95% confidence interval (CI). We assessed the quality of evidence using GRADE methodology (31). We explored heterogeneity between studies by performing predetermined subgroup analyses to investigate whether certain factors influenced treatment effect and assessed statistical heterogeneity using the Chi2 and I2 statistics. We considered Chi2 <0.1 or I2 > 50% as significant heterogeneity (32).
Results: Thirteen RCTs (enrolling 1341 patients) met inclusion criteria (22-26,33-40). We judged two studies to be at high risk (25,45), five to be low risk (25,26,35-37) and six to be unclear (22,23,33,34,38,39). Prokinetic agents significantly reduced feeding intolerance (RR 0.73, 95% CI 0.55, 0.97, P=0.03), with a number needed to treat of 12. Prokinetics also significantly reduced the risk of developing high gastric residual volumes (GRVs) (0.69, 95% CI 0.52, 0.91, P=0.009) and increased the success of post-pyloric feeding tube placement (RR 1.60. 95% CI 1.17, 2.21, P=0.004). There was no statistical improvement in the risk of vomiting, mortality, diarrhea, or intensive care unit (ICU) LOS.  In the subgroup analysis, when comparing prokinetics, erythromycin reduced the amount of feeding intolerance compared to metoclopramide (RR 0.64, 95% CI 0.44, 0.96, P=0.03; RR 1.80, 95% CI 0.43, 7.59, P=0.73, respectively) but did not shorten LOS, decrease mortality, or prevent vomiting and pneumonia.
Conclusion: Moderate quality evidence showed that prokinetic agents, particularly erythromycin, reduced feeding intolerance and high GRVs in critically ill patients. However, the impact on other important outcomes such as pneumonia, mortality, ICU LOS and potential side effects of the prokinetics is unclear.  

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