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The pressure–volume index (PVI) can be used to assess the cerebrospinal fluid dynamics and intracranial elastance in critically ill brain injured patients. The dependency of PVI on the state of cerebral autoregulation within the physiologic range of cerebral perfusion pressure (CPP) can be described by mathematical models that account for changes in cerebral blood volume during PVI testing. This relationship has never been verified clinically using direct PVI measurement and independent cerebral autoregulation assessment. PVI and cerebral autoregulation were prospectively assessed in a cohort of 19 comatose patients admitted to an academic intensive care unit in Brescia, Italy. None. PVI was measured injecting a fixed volume of 2 ml of 0.9% sodium chloride solution into the cerebral ventricles through an intraventricular catheter. Cerebral autoregulation was assessed using transcranial Doppler transient hyperaemic response (THR) test. Fifty-nine PVI assessments and 59 THR tests were performed. Mean PVI was 20.0 (SD 10.2) millilitres in sessions when autoregulation was intact (THR test ≥1.1) and 31.6 (8.8) millilitres in sessions with defective autoregulation (THR test <1.1) (ΔPVI = 11.7 ml, 95% CI = 4.7–19.3 ml; P = 0.002). Intracranial pressure, CPP and brain CT findings were not significantly different between the measurements with intact and disturbed autoregulation. Cerebral autoregulation status can affect PVI estimation despite a normal CPP. PVI measurement may overestimate the tolerance of the intracranial system to volume loads in patients with disturbed cerebral autoregulation. [ABSTRACT FROM AUTHOR]