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 13 C 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 Splanchnic hypoperfusion 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 Clin Nutr. 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 CO 2 production.

33. Concerns with erythromycin Bacterial resistance Cardiac toxicity Drug interactions

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