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

Research output: Contribution to journalArticlepeer-review


  • Jerry P Nolan
  • Charles D Deakin
  • Chen Ji
  • Andy Rosser
  • Ranjit Lall
  • Gavin D Perkins

Colleges, School and Institutes

External organisations

  • Royal United Hospital Bath NHS Trust, Royal United Hospital, Avon, Bath, Somerset, UK.
  • South Central Ambulance Service NHS Foundation Trust, Otterbourne, SO21 2RU, UK; NIHR Southampton Respiratory Biomedical Research Unit, Southampton, SO16 6YD, UK.
  • Warwick University
  • West Midlands Ambulance Service University NHS Foundation Trust, Brierley Hill, West Midlands, DY5 1LX, UK.
  • Sandwell and West Birmingham Hospitals (SWBH) and University Hospitals Birmingham (UHB) NHS Trust, Birmingham, United Kingdom.


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).


Original languageEnglish
Pages (from-to)954-962
Number of pages9
JournalIntensive Care Medicine
Issue number5
Publication statusPublished - May 2020