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