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Original research
Prehospital opioid dose and myocardial injury in patients with ST elevation myocardial infarction
  1. Himawan Fernando1,2,3,
  2. Ziad Nehme4,5,
  3. Karlheinz Peter1,3,
  4. Stephen Bernard5,6,
  5. Michael Stephenson5,
  6. Janet Bray4,
  7. Peter Cameron4,
  8. Andris Ellims1,
  9. Andrew Taylor1,
  10. David M Kaye1,7,
  11. Karen Smith4,5 and
  12. Dion Stub1,4,7
  13. for the AVOID investigators
  1. 1Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia
  2. 2Central Clinical School, Monash University, Melbourne, Victoria, Australia
  3. 3Atherothrombosis and Vascular Biology, Baker Heart Research Institute, Melbourne, Victoria, Australia
  4. 4Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
  5. 5Research & Evaluation, Ambulance Victoria, Doncaster, Victoria, Australia
  6. 6Intensive Care Unit, Alfred Hospital, Melbourne, Victoria, Australia
  7. 7Heart Centre, Baker Heart Research Institute, Melbourne, Victoria, Australia
  1. Correspondence to Dr Dion Stub; d.stub{at}


Objective To characterise the relationship between opioid dose and myocardial infarct size in patients with ST elevation myocardial infarction (STEMI).

Methods Patients given opioid treatment by emergency medical services with confirmed STEMI were included in this secondary, retrospective cohort analysis of the Air versus Oxygen in Myocardial Infarction (AVOID) study. Patients with cardiogenic shock were excluded. The primary endpoint was comparison of cardiac biomarkers as a measure of infarct size based on opioid dose (low ≤8.75 mg, intermediate 8.76–15 mg and high >15 mg of intravenous morphine equivalent dose).

Results 422 patients were included in the analysis. There was a significantly higher proportion of patients with Thrombolysis in Myocardial Infarction (TIMI) 0 or 1 flow pre-percutaneous coronary intervention (PCI) (94% vs 81%, p=0.005) and greater use of thrombus aspiration catheters (59% vs 30%, p<0.001) in the high compared with low-dose opioid group. After adjustment for potential confounders, every 1 mg of intravenous morphine equivalent dose was associated with a 1.4% (95% CI 0.2%, 2.7%, p=0.028) increase in peak creatine kinase; however, this was no longer significant after adjustment for TIMI flow pre-PCI.

Conclusions Our study suggests no benefit of higher opioid dose and a dose-dependent signal between opioid dose and increased myocardial infarct size. Prospective randomised controlled trials are required to establish causality given that this may also be explained by patients with a greater ischaemic burden requiring higher opioid doses due to more severe pain. Future research also needs to focus on strategies to mitigate the opioid–P2Y12 inhibitor interaction and non-opioid analgesia to treat ischaemic chest pain.

  • platelet activation
  • coronary intervention (PCI)
  • myocardial ischaemia and infarction (IHD)
  • antiplatelet treatment

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  • Contributors DS conceived and designed this research analysis. HF, ZN and DS acquired the data and performed the statistical analysis. KP, SB, MS, JB, PC, AE, AT, DKM, KS and DS handled funding and supervision of the AVOID trial and critical review of the current manuscript for key intellectual content which was drafted by HF and DS.

  • Funding The AVOID study was funded by grants from Alfred Foundation, FALCK foundation and Paramedics Australia.

  • Competing interests ZN is funded by a National Health and Medical Research Council Early Career Fellowship (#1146809). DS is funded by National Heart Foundation Fellowship and Viertel Foundation Grant.

  • Patient consent for publication Not required.

  • Ethics approval Alfred Health Human Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. Deidentified data generated from the AVOID study requires ethics approval prior to being made available.

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