L . Andersen et al .: J Extra Corpor Technol 2023 , 55 , 209 – 217 215
Figure 7 . Effect of cyclic pump flow changes ( upper panel ) on arterial blood pressure ( ABP , middle panel ), and cerebral blood flow velocity ( CBFV ) in the middle cerebral arteries ( lower panel ) at PaCO 2 of 40 mmHg ( 5.3 kPa ) in a single patient undergoing cardiopulmonary bypass . Reprinted with permission from the owner Springer Nature : Ševerdija EE , Gommer ED , Weerwind PW , Reulen JP , Mess WH , Maessen JG ( 2015 ) Assessment of dynamic cerebral autoregulation and cerebral carbon dioxide reactivity during normothermic cardiopulmonary bypass . Med Biol Eng Comput 53 ( 3 ), 195 – 203 .
mechanisms alone as CA refers to a complex interaction between all involved [ 11 ].
Clinical outcome related to the COx index
The amount of evidence showing an absolute association between results from monitoring the COx index and clinical outcomes is limited . Brown and colleagues assessed CA by means of transcranial Doppler in a group of cardiac surgical patients requiring the use of CPB [ 46 ]. A total of 20.6 % of the patients were observed with episodes of CA dysfunction . The lower mean arterial blood pressure limit of CA was targeted prior to CPB using mean velocity index ( Mx ) > 0.4 – equivalent to the COx threshold . The computed blood pressure target ranged 35.0 – 97.5 mmHg , which may seem extraordinary . Patients randomized to maintain MAP above the lower designated blood pressure limit of CA during CPB were less likely to develop postoperative delirium . Whether this was caused by the MAP target or a longer duration of normal CA was unfortunately not discussed . These findings agree with those reported by Chan and Aneman [ 47 ]. In this prospective study , COx was registered on the two first following postoperative days . The COx index was significantly higher among patients diagnosed with postoperative delirium on postoperative Day 1 : 0.270 ± 0.199 vs . 0.180 ± 0.142 ( P = 0.044 ). The magnitude of these COx indices is however very low , which generally would not indicate disturbed CA . Hori and co-workers showed how a blood pressure below the lower limit of preserved CA observed in the intensive care unit was positively correlated with the release of the brain-specific injury biomarker glial fibrillary acidic protein ( GFAP ) [ 48 ]. Of note is that blood pressure targets for the lower limit of preserved CA were calculated during CPB , while outcome measures were performed postoperatively . This is once again an example of an indirect conclusion being drawn from an association between blood pressure and outcome ; not how fluctuations of CA per se correlated with the outcome – in this case the release of GFAP . Blood pressure excursions below the lower limit of CA during CPB have also been shown to be associated with major morbidity and intraoperative mortality [ 49 ]. Using a composite variable to identify risk factors associated with abnormal CA makes it difficult to verify a causal relationship . In addition , accepting COx 0.3 as the threshold of abnormal CI involves a significant degree of uncertainty , which would only explain about 10 % of the observed correlation between the measured MAP and CBF . Among 450 patients , 83 experienced complications according to the a priori definition . The risk of developing complications was independently associated with the area under the curve for the duration of MAP below the lower limit of preserved CA .
Closing remarks
Monitoring the CA by measuring the correlation between CBF and MAP is intriguing . The method aims to identify a blood pressure limit at which MAP and CBF become correlated . Numerous publications verify that this is possible and more importantly that the information can be used to protect patient groups against a variety of different adverse complications . The key question is whether this blood pressure limit really is a reliable marker of CA ? To answer this question , we need investigations to verify that the blood pressure limit can be used to successfully tailor and maintain CA in real-time , i . e ., if MAP drops below the targeted limit , the COx registration should signal , and additionally verify that CA is restored by blood pressure adjustments . To the best of our knowledge , no such verification publication exists . Until then , we believe that the information obtained from the COx index should be thoroughly scrutinized before introduction into clinical practice .
Conflict of interest The authors declare no conflict of interest
Funding
This research received no specific grant from any funding agency in the public , commercial , or not-for-profit sectors .
Data availability
Data supporting the results from this study are available on reasonable request from the authors .
Ethics
The Regional Ethical Review Board in Umeå approved the study protocol ( DNr-2018 / 436-31 ). Patient consent was waived .