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

Background

• Gastrointestinal motility in the critically

ill

• Erythromycin as a prokinetic

• Absorption in the small intestine

Aims

• Primary– Glucose absorption

• Secondary– Blood glucose– Lipid absorption– Small intestinal transit

Methods

• Randomised, double-blinded, crossover

study

• Ethics Committee approval

• Written informed consent from next of kin

• ANZCTR number 12610000615088

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

Glucose absorption

• 3-O-Methylglucose (3-OMG)

Lipid absorption

• 13C Triolein

Small intestinal transit

• Technetium-99m

Statistics

• Sample size, pilot data

• Power calculation

• Non parametric tests

• Time points – ‘early’ and ‘overall’

ResultsNumber of patients = 20

Age (years) 53 (20 – 77)

Gender (M:F) 14 : 6

Body Mass Index (kg/m2) 28.7 (20.5 – 42.2)

APACHE II 19 (8 – 38)

Days in ICU 5 (2 -15)

Tolerating feeds (n)YesNo

713

Admission Diagnosis (n) Pneumonia or Sepsis (4)Multi-trauma (4)Cardiac (4)Neurosurgical (2)Other (6)

Results

Results

Results

Results

Summary

• Glucose absorption

• Blood glucose level

• Lipid absorption

• Small intestinal transit

Limitations

• Interim analysis

• Single dose of erythromycin

• Applicability to other nutrients

Future directions

• Additional number of subjects

• Use of non-antibiotic motilides

• Small intestinal biopsy

Conclusion

• Erythromycin has no effect on nutrient

absorption in critically ill patients

Motilin and the MMC

Nutrient absorption in critical illness

• Disordered flow of chyme

• Impaired mucosal function

• Splanchnic hypoperfusion

• Small intestinal transit time

• Possible reduction in SGLT1

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

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)

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 CO2 production.

Concerns with erythromycin

• Bacterial resistance

• Cardiac toxicity

• Drug interactions

Deane, et al.

Critical Care & Resuscitation 2009

Healthy control

Critically ill patient

Delayed gastric emptying in the critically ill