Sites and Patients

The trial was conducted in 65 UK National Health Service (NHS) adult, general, ICUs that participate in the Case Mix Programme—the national clinical audit for adult ICUs across England, Wales, and Northern Ireland. Patients aged 65 years or older admitted to a participating ICU were eligible if they were randomized within 6 hours of commencing a vasopressor infusion (to minimize exposure to vasopressors prior to randomization) for vasodilatory hypotension, with adequate fluid resuscitation (as assessed by the treating clinician) completed or ongoing and vasopressors were expected to continue for 6 hours or more. In an earlier version of the protocol, randomization was permitted from the point of making the decision to commence a vasopressor infusion (Figure 1). Exclusion criteria included contraindications to permissive hypotension (eMethods in Supplement 2).

^aAs assessed by the treating clinician.

^bSome patients met more than 1 criterion.

Screening was conducted by the clinical-research teams at each ICU. Randomization occurred as soon as possible once eligibility was confirmed. Patients were allocated in a 1:1 ratio, via a concealed central 24-hour telephone-web randomization system, to permissive hypotension or usual care. Randomization was stratified by site using permuted blocks with variable block lengths (of 4, 6, and 8).