Erythromycin for Gastric Emptying in Patients Undergoing General Anesthesia for Emergency Surgery

Czarnetzki. JAMA Surg. 2015; 150:730-7. doi:10.1001/jamasurg.2015.0306

Clinical Question

  • In adult patients undergoing general anaesthesia for emergency surgery, does pre-medication with erythromycin compared to placebo reduce the volume of gastric content?


  • Single-centre, randomised, placebo-controlled trial
  • Double blinded
  • Randomisation sequence generated by hospital pharmacy and patients allocated on arrival in the operating room
  • Concealment of sequence not specified
  • Stratified by trauma status (trauma vs non-trauma)
  • A power calculation was based upon a 30% baseline incidence of a clear stomach in the placebo group and an expected 80% incidence in the erythromycin group (absolute risk reduction 50%)
    • 90% power
    • Significance level 0.05
    • 40 patients per group were required (increased to 50 to allow for lost data)
  • However, recalculation of power calculation was performed as overall observed incidence of a clear stomach was 76%
    • Maintained 90% and significance level 0.05
    • Expected absolute risk reduction reduced to 30%
    • Total 132 patients randomised
  • Intention-to-treat analysis


  • Single university hospital in Geneva
  • March 2009 – April 2013


  • Inclusion: Adult patients requiring emergency surgery under general anaesthesia
  • Exclusion: ASA > 3; GCS < 13; allergy to erythromycin or use of interacting drugs; significant comorbidity (including porphyria, liver or renal disease, severe asthma, exacerbated COPD, pneumonia, acute coronary disease, decompensated heart disease, aortic aneurysm, oesophageal disease, recent gastric surgery, obstructive ileus); presence of gastric tube or need for immediate surgical intervention; pregnancy or breastfeeding
  • 569 patients assessed; 132 patients included; no lost data


  • Erythromycin
    • 3 mg/kg erythromycin (made as 3mg/ml in NaCl 0.9% so that 1ml/kg solution was given) administered over 5 minutes given 15 minutes prior to induction of anaesthesia


  • Placebo
    • 1ml/kg NaCl 0.9% as matched placebo administered over 5 minutes given 15 minutes prior to induction of anaesthesia

Management common to both

  • Three minutes pre-oxygenation
  • “Classic rapid-sequence procedure”
    • Thiopental, propofol or etomidate
    • Followed by suxamethonium or rocuronium
  • Maintenance at anaesthetist’s discretion
  • Gastroscopy by senior gastroenterologist


  • Primary outcome:
    • Residual of less than 40 ml gastric liquid and the absence of solid food
      • Erythromycin 80% vs Placebo 64%
      • Risk ratio 1.26 (95% CI 1.01–1.57; P = 0.0518 using Fisher’s Exact)
        • (RR > 1.0 favours erythromycin)
      • Absolute risk reduction (ARR) 16.7% (95% CI 1.61–31.7%)
      • Number needed to treat (NNT) 6
      • Fragility Index 0 (zero)
    • Sensitivity analysis with strict definition: completely empty stomach
      • Erythromycin 62% vs Placebo 36%
      • Risk ratio 1.67 (95% CI 1.15–2.42; P = 0.0055)
      • ARR 24.2% (95% CI 7.7–40.8%)
      • NNT 5
  • Sub-group analysis:
    • Trauma: a statistically significant association between erythromycin and endoscopy findings was not found
    • Non-trauma: a statistically significant association between erythromycin and endoscopy findings was found
  • Secondary outcome: (as Erythromycin vs Placebo)
    • Median acidity of residual gastric content:pH 2 vs 6 (P = 0.002)
    • Median volume of residual gastric content: 27.5 ml vs 43.5 ml (P = 0.38)
  • Safety outcomes: (as Erythromycin vs Placebo)
    • Stomach cramps: 30% vs 6% (P < 0.001; absolute risk increase (ARI) 24.2%;  number needed to harm (NNH) 5)
    • Nausea: 23% vs 3% (P < 0.001; ARI 19.7%; NNH 6)
    • Vomiting: 1.5% vs 0% (P = 1.0)

Authors’ Conclusions

  • Erythromycin reduces residual gastric volume in patients undergoing emergency surgery under general anaesthesia with an acceptable side effect profile


  • Randomised and placebo-controlled
  • Good randomisation method, concealment of allocation and blinding of patient, clinician and outcome assessor
  • Revision of power calculation without revealing randomisation sequence
  • Intention to treat analysis and complete follow-up


  • 569 patients screened for inclusion over 4 years in university hospital – is there a selection bias risk?
  • Surrogate end-point
    • Arguably regurgitation or aspiration should be the clinically important end-point but harder to study as rare
    • It is difficult to conclude that lower residual volumes correlate to reduced aspiration volumes
    • The only clinically meaningful endpoints measured were nausea and stomach cramps which were higher in the intervention arm.
  • In non-trauma stratum, majority were undergoing appendicectomy or cholecystectomy – whilst these are common and may be majority of workload, this does reduce generalisability to other patient groups
  • Numbers in trauma and non-trauma subgroups were two small for meaningful interpretation
  • Trial excluded all high risk patient groups – findings are probably not generalisable to ASA > 3 patients or those critically unwell not requiring surgery

The Bottom Line

  • This single centre RCT has methodological concerns that reduce the internal validity and external generalisability
  • Erythromycin may reduce residual gastric content and acidity but this trial does not demonstrate sufficient statistical significance to reject the null hypothesis
  • Any benefit occurs at the expense of unpleasant side effects with equal incidence to the intended benefit
  • Whilst the authors should be commended for thinking laterally and investigating this novel idea, I shall not be using erythromycin prior to rapid sequence induction of anaesthesia

External Links


Summary author: Duncan Chambler
Summary date: 21 June 2016
Peer-review editor: Celia Bradford

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.