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Intraosseous versus intravenous administration of adrenaline in patients with out-of-hospital cardiac arrest: a secondary analysis of the PARAMEDIC2 placebo-controlled trial

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Abstract

Purpose

To compare the effectiveness of the intravenous (IV) and intraosseous (IO) routes for drug administration in adults with a cardiac arrest enrolled in the Pre-Hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) randomised, controlled trial.

Methods

Patients were recruited from five National Health Service Ambulance Services in England and Wales from December 2014 through October 2017. Patients with an out-of-hospital cardiac arrest who were unresponsive to initial resuscitation attempts were randomly assigned to 1 mg adrenaline or matching placebo. Intravascular access was established as soon as possible, and IO access was considered if IV access was not possible after two attempts.

Results

Among patients with out-of-hospital cardiac arrest, 3631 received adrenaline and 3686 received placebo. Amongst these, 1116 (30.1%) and 1121 (30.4%) received the study drug via the IO route. The odds ratios were similar in the IV and IO groups for return of spontaneous circulation (ROSC) at hospital handover [adjusted odds ratio (aOR) 4.07 (95% CI 3.42–4.85) and (aOR 3.98 (95% CI 2.86–5.53), P value for interaction 0.90]; survival to 30 days [aOR 1.67 (1.18–2.35) versus 0.9 (0.4–2.05), P = 0.18]; and favourable neurological outcome [aOR 1.39 (0.93–2.06) versus 0.62 (0.23–1.67), P = 0.14].

Conclusion

There was no significant difference in treatment effect (adrenaline versus placebo) on ROSC at hospital handover between drugs administered by the intraosseous route or by the intravenous route. We could not detect any difference in the treatment effect between the IV and IO routes on the longer term outcomes of 30-day survival or favourable neurological outcome at discharge (ISRCTN73485024).

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Funding

The trial was funded by the Health Technology Assessment Programme of the National Institute for Health Research (NIHR) and supported by NIHR Applied Research Centre (ARC) West Midlands, UK, NIHR Comprehensive Research Network, Out-of-Hospital Cardiac Arrest Registry, which is funded by the British Heart Foundation and Resuscitation Council UK; and by Health Care Wales.

Author information

Authors and Affiliations

  1. Warwick Clinical Trials Unit, University of Warwick, Coventry, CV4 7AL, UK

    Jerry P. Nolan, Chen Ji, Ranjit Lall & Gavin D. Perkins

  2. Royal United Hospital, Bath, BA1 3NG, UK

    Jerry P. Nolan

  3. South Central Ambulance Service NHS Foundation Trust, Otterbourne, SO21 2RU, UK

    Charles D. Deakin

  4. NIHR Southampton Respiratory Biomedical Research Unit, Southampton, SO16 6YD, UK

    Charles D. Deakin

  5. Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, B15 2TT, UK

    Simon Gates

  6. West Midlands Ambulance Service University NHS Foundation Trust, Brierley Hill, DY5 1LX, West Midlands, UK

    Andy Rosser

  7. Heartlands Hospital, University Hospitals Birmingham, Birmingham, B9 5SS, UK

    Gavin D. Perkins

Authors
  1. Jerry P. Nolan
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  2. Charles D. Deakin
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  3. Chen Ji
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  4. Simon Gates
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  5. Andy Rosser
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  6. Ranjit Lall
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  7. Gavin D. Perkins
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Contributions

GDP, CJ, RL, SG, and Rogers had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: JPN, GDP, CDD, CJ, RL, and SG. Acquisition, analysis, or interpretation of data: GDP, JPN, CDD, CJ, RL, SG, and AR. Drafting of the manuscript: JPN, GDP, CDD, CJ, and RL. Critical revision of the manuscript for important intellectual content: JPN, GDP, CDD, CJ, RL, SG, and AR. Statistical analysis: CJ, RL, SG. Obtained funding: GDP, JPN, CDD, RL, and SG. Supervision: GDP.

Corresponding author

Correspondence to Jerry P. Nolan.

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Conflicts of interest

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the NIHR for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; GDP, CD, and JN have volunteer roles with the International Liaison Committee on Resuscitation, European (GDP, JN), and UK (GDP, JN, CD) Resuscitation Councils.

Role of the funder/sponsor

The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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The views and opinions expressed in this report are those of the authors and do not necessarily reflect those of the Health Technology Assessment Programme, the NIHR, National Health Service, or the Department of Health and Social Care.

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Nolan, J.P., Deakin, C.D., Ji, C. et al. Intraosseous versus intravenous administration of adrenaline in patients with out-of-hospital cardiac arrest: a secondary analysis of the PARAMEDIC2 placebo-controlled trial. Intensive Care Med 46, 954–962 (2020). https://doi.org/10.1007/s00134-019-05920-7

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