Invos

Parameters measuring CBF and brain tissue oxygenation were the predefined study endpoints.
Direct measurement of CBF (primary endpoint): The course of CBF, was measured by an intracerebral thermodilution probe (Q-Flow 500®) located in the right frontal cortex. The probe was placed 1.5 cm anterior to the external ventricular drainage and was monitored by a Bowman Perfusion Monitor® (Hemedex™, Cambridge, MA, USA). To obtain a continuous measurement and avoid recalibration during the study intervention, the automatic calibration was paused during the time of the study intervention^{10 (link)}.
Transcranial Doppler sonography (TCD): Prior to the beginning of each study intervention, baseline measurements of TCD were made. At each time-point during the study intervention, TCD measurements were repeated. Measurements were conducted by a well-trained medical technician otherwise not involved in the study procedures with an experience of over 15 years of TCD measurements.
Cerebral tissue oxygen saturation (S_tiO₂) (secondary endpoint): S_tiO₂ was measured by bilateral near-infrared spectroscopy (NIRS) electrodes (INVOS®, Covidien, Neustadt/Donau, Germany), which were attached on both sides of the forehead. A baseline value was set prior to the intervention to which the following measurements (every 15 min for 2 h) were compared.

Transcranial cerebral oximetry non-invasively monitors cerebral oxygen saturation (rSO₂) in the frontal lobes of the brain and has been shown to correlate with cerebral venous oxygen saturation, which is traditionally considered the 'gold-standard’ for determining oxygen delivery/consumption [29 (link)]. Accepted thresholds for cerebral ischemia are a rSO₂ of <50% or a decline of >20% [30 (link)]. This will be applied during the intra-operative period of the SANITY study with use of INVOS™ (Covidien, Boulder, CO) specifically to monitor the cerebral oxygen delivery compromise associated with the procedure, and in particular with rapid ventricular pacing [31 ,32 ].