The effects of erythromycin on nutrient absorption in critical illness

1. The effects of erythromycin on nutrient absorption in critical illness Dr Gerald Wong FANZCA FCICM Gerald Wong, Anna DiBartolomeo, Marianne Chapman, Matthew Summers, Anthony Zaknic, Max Bellon, Anne Maddox, Robert Fraser, Michael Horowitz, Adam Deane Intensive Care Unit, Royal Adelaide Hospital Discipline of Anaesthesia and Intensive Care, University of Adelaide National Health and Medical Research Council of Australia Centre for Clinical Research and Excellence in Nutritional Physiology and Outcomes, Adelaide, South Australia Department of Nuclear Medicine, Royal Adelaide Hospital

2. Background • Gastrointestinal motility in the critically ill • Erythromycin as a prokinetic • Absorption in the small intestine

3. Aims • Primary • Glucose absorption • Secondary • Blood glucose • Lipid absorption • Small intestinal transit

4. Methods • Randomised, double-blinded, crossover study • Ethics Committee approval • Written informed consent from next of kin • ANZCTR number 12610000615088

5. Methods • Study Drug = Erythromycin 200mg or Placebo from t = -20 mins to 0 min • Study feed = 60mls Ensure from t = 0 min to t = 30 mins • * Blood sample for measurement of 3-OMG and Glucose • # Breath sample for measurement of Triolein absorption

6. Glucose absorption • 3-O-Methylglucose (3-OMG)

7. Lipid absorption • 13C Triolein

8. Small intestinal transit • Technetium-99m

9. Statistics • Sample size, pilot data • Power calculation • Non parametric tests • Time points – ‘early’ and ‘overall’

10. Results

11. Results

12. Results

13. Results

14. Results

15. Summary • Glucose absorption • Blood glucose level • Lipid absorption • Small intestinal transit

16. Limitations • Interim analysis • Single dose of erythromycin • Applicability to other nutrients

17. Future directions • Additional number of subjects • Use of non-antibiotic motilides • Small intestinal biopsy

18. Conclusion • Erythromycin has no effect on nutrient absorption in critically ill patients

22. Motilin and the MMC

25. Nutrient absorption in critical illness • Disordered flow of chyme • Impaired mucosal function • Splanchnichypoperfusion • Small intestinal transit time • Possible reduction in SGLT1

30. Inclusion eligibility • Patients admitted to a tertiary referral ICU • Aged 18 years or older • Likely to remain mechanically ventilated > 72 hours • Receiving or suitable to receive post-pyloric enteral nutrition

31. Exclusion criteria • Pregnancy • Contraindication to enteral feeding • Previous surgery on the oesophagus, stomach , or duodenum • History of diabetes mellitus • Contraindication to opiate sedation • Receiving erythromycin at antimicrobial dose • Liver dysfunction (ALT > 3x ULN)

32. Lipid absorption (Deane, et al ClinNutr. 2010) Potential for intrasubject variability and/or inaccuracy using isotope breath tests in the critically ill. Measurement inaccuracies may occur because of impairment of (1) absorption or (2) hepatic metabolism, as well as (3) variations in endogenous CO2 production.

33. Concerns with erythromycin • Bacterial resistance • Cardiac toxicity • Drug interactions

37. Delayed gastric emptying in the critically ill Healthy control Critically ill patient Deane, et al. Critical Care & Resuscitation 2009