Reply to Siric et al.

We are delighted that our study on the value of higher perfusion pressures during cardiopulmonary bypass (CPB) to prevent delirium [1] creates great interest and discussion. The remarks made by the group of F. Siric indicate that the topic is important and further research is needed to answer the remaining questions [2].

We want to focus on the remarks brought up by Siric et al. point by point:

1. Using one cognitive test only is a clear limitation of the study protocol. However, for the main outcome parameter rate of delirium, we relied on two things: decline in the Mini-Mental State Examination plus positive evaluation by a consultant specialist. In a future larger trial, we intend to use two different tests and various points of time in the postoperative course rather than only one early postoperative measurement.

2. We screen for cerebrovascular disease routinely in our clinic and will not allow patients with a stenosis of the internal carotid artery of >50% being perfused with low pressures. That is why those patients could not be randomized.

3. Since we are aware of the potential harms of side biting clamping of the aorta we systematically avoid additional clamping in our coronary artery bypass grafting patients with the use of CPB and do all proximal anastomosis during cardiac arrest.

4. We did not differentiate the transfusion requirements by the timing (during CPB run or thereafter). However, in terms of oxygen transport capacity, we thoroughly analysed the haematocrit and it was not different between the groups at any time. The haematocrit was kept >20% during the whole extracorporeal circulation.

5. Although not impossible, we doubt that higher perfusion pressures during CPB will have an effect on postoperative bleeding. As correctly stated by Siric et al., the cohort size in the trial might not be sufficient to rule out this side effect of higher CPB perfusion pressures.

6. For this trial, we do only have absolute values from near-infrared spectroscopy at given points of time. Using this method, we indented to find evidence for our hypothesis that a cerebral hypoperfusion resulting from low pressure perfusion might be the reason for cognitive decline. However, we failed to proof this effect. We will take the excellent remark into consideration and look for more sophisticated values of cerebral oxygenation measurements in future.

The remarks on other tools to modify the oxygen delivery and consumption of the brain are well taken. However, the modification of several factors is not advisable in a clinical trial and would make the interpretation of results difficult. Obviously, more research on the topic is needed to correctly answer permanent questions in how to avoid postoperative delirium in patients operated with the use of CPB.

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