Strengths and limitations
delirium, blood loss
BLOOD LOSS, SECONDARY, PATHOGENESIS
This secondary analysis was conducted using a randomised, double-blind, placebo-controlled trial. To our knowledge, this is the first clinical trial to investigate the influence of intra- and postoperatively administered dexmedetomidine on the perioperative course of AChE and BChE. Overall, the results of the present study strengthen the role of the cholinergic system in delirium pathogenesis and at the same time suggest a regulatory effect of dexmedetomidine on the cholinergic system.The present study did not show a significant difference in postoperative changes of AChE activity between dexmedetomidine and placebo treated patients. This may be due to a relatively small population size. Administrative and technical limitations led to incomplete follow-up measurements in some subjects. Moreover, the trial was powered for the primary outcome of POD incidence on the one hand, on the other hand, baseline values of both groups showed large interquartile ranges pointing towards high variation. We used a portable point-of-care photometer, which was originally designed for the analysis of ChE inhibition in organophosphate poisoning.Cholinesterase activity is subject to a circadian rhythmTherefore, preoperative values are likely influenced by circadian fluctuation. In our opinion, strict timing of AChE and BChE measurements could yield more homogenous results and significant between-group differences. Considering the existing difference between the groups in terms of their baseline esterase activities (AChE: 44.80 vs. 40.5 and BChE: 3088 vs. 2512), we have to assume that the preoperative values were probably influenced by circadian fluctuations. In our opinion, strict timing of AChE and BChE measurements could lead to more homogeneous baseline activity values and significant differences in activity progression between the groups.A further subdivision of the groups into patients who actually developed delirium or remained delirium-free was not made due to the already very small group sizes (a total of 14 with delirium, 3 of which were in the dexmedetomidine group). However, such an analysis would probably be helpful with a larger population to obtain more informative results. There is also limited interpretation of cholinesterase activities in the groups with and without delirium up to the first postoperative day (Fig. It should also be considered that our patients were recruited from two distinct populations: major abdominal surgeries and coronary artery bypass graft surgeries. One could suppose that these populations are distinct from one another, for instance in regard to perioperative blood loss and subsequent transfusions which is usually higher in cardiac surgeries. It has already been demonstrated by John and her colleagues that these factors alter the course of perioperative cholinesterases in patients who underwent cardiac surgeryAs pro-inflammatory markers such as CRP were not recorded in the primary database, we could not analyse the relationship between cholinesterase activity, inflammatory markers and dexmedetomidine.There is only limited literature about the regulation of cholinesterases, which makes it challenging to examine homogenous populations. A further limitation results from the lack of comparable studies on the effect of dexmedetomidine on cholinesterases. Accordingly, many reference studies have a different experimental design and comparability to our study is limited.Therefore, we regard this secondary analysis rather as hypothesis-generating and we advocate for further investigations that are statistically powered for this question and that examine homogenous populations.