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1
In TRICYCLE, the median 5.2-hour interval ran from earliest hospital presentation with sepsis or septic shock to randomization, not from vasopressor-threshold attainment.
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2
TRICYCLE allowed enrollment up to 12 hours after the vasopressor eligibility threshold, but this was a maximum window, not the actual threshold-to-randomization interval.
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3
Although randomization vasopressor doses were comparable in TRICYCLE and ATHOS-3, enrollment timing differed, so similar doses do not establish comparable shock duration or stage.
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4
Vasopressor dose reflects both elapsed time and the speed and severity of hemodynamic deterioration, so a high dose alone does not show that treatment was delayed.
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5
The authors characterize TRICYCLE as evaluating early multimodal vasopressor therapy and argue that early treatment should not be defined by a single vasopressor dose cutoff.
