A randomised controlled trial tested whether intramuscular adrenaline, the standard first-line treatment for anaphylaxis, effectively reverses severe hypotension caused by histamine infusion in healthy volunteers. Despite achieving plasma adrenaline concentrations considered therapeutic, the injections failed to produce a sustained pressor response in most participants, performing indistinguishably from placebo. Only 25% of participants showed a transient blood pressure recovery, which was not maintained. The findings challenge the longstanding guideline recommendations based on expert consensus rather than controlled human data, highlighting a critical need to re-evaluate the role of adrenaline in histamine-mediated shock and consider more potent interventions.

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