Non-pulsatile blood flow is associated with enhanced cerebrovascular carbon dioxide reactivity and an attenuated relationship between cerebral blood flow and regional brain oxygenation

Abstract

BackgroundSystemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO2 vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO2) that determine cerebral oxygen delivery are not uncommon—especially when CO2 is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO2 reactivity (CVR) and regional brain oxygenation (rSO2).MethodsIn this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO2 was determined during step changes of PaCO2 between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO2 alterations were determined for each flow mode. Each patient served as her own control.ResultsMCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO2 slope during non-pulsatile flow was 14.4 cm/s/mmHg [CI 11.8–16.9] and 10.4 cm/s/mmHg [CI 7.9–13.0] after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg, p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO2 and ΔMCAv was less pronounced during non-pulsatile flow.ConclusionsNon-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO2/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed.Trial registrationThe study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).

Supporting the circulation, but injuring the brain: the (still unsolved) threat and paradox of extracorporeal life support

“…This study shows a rate and types of events in accordance with a recent Extracorporeal Life Support Organization (ELSO) Registry report, 2 that is a prevalence higher than 15% and with ischemic lesions higher than hemorrhage, with a major impact, as expected, on ultimate patient prognosis. These findings are also in accordance to other recent publications 3–6 confirming, unfortunately, that such adverse events are frequent, and, most likely, even more common than observed, as shown by an important study on post-mortem assessment of ECLS patients, with 50% of the brain-related injuries not diagnosed pre-mortem. 7…”

“…Several important studies have shown some clues and highlighted predisposing factors which should be taken into consideration (Table 1). [1][2][3][4][5][6][7][8][9][10][11][12] Furthermore, it is also of paramount importance to use continuous multimodal monitoring and institute prompt advanced imaging. 13 But can we really improve the fate in this respect?…”

Risk Factors for Delayed Neurocognitive Recovery According to Brain Biomarkers and Cerebral Blood Flow Velocity

“…BFV during bypass becomes nonpulsatile, which may be one of the risk factors of various complications [ 51 , 52 ]. Even short-term nonpulsatile flow conditions rapidly affect cerebral circulation [ 53 ]. Patients with low left ventricular ejection fraction receiving emergent VA-ECMO could potentially be vulnerable for cerebral insults, especially during hypothermic and hypocapnic states [ 53 ].…”

“…Even short-term nonpulsatile flow conditions rapidly affect cerebral circulation [ 53 ]. Patients with low left ventricular ejection fraction receiving emergent VA-ECMO could potentially be vulnerable for cerebral insults, especially during hypothermic and hypocapnic states [ 53 ]. For this reason, it is very important to use multimodal monitoring, which may help to minimize the incidence of adverse neurologic reactions.…”

Development of a Pulsatile Flow-Generating Circulatory Assist Device (K-Beat) for Use with Veno-Arterial Extracorporeal Membrane Oxygenation in a Pig Model Study

“…A pulsatile flow pattern is important not only to ensure an efficient circulatory flow throughout body but also to maintain optimal end-organ function. Loss of pulsatility is associated with neurological complications and peripheral circulatory failure [ 7 , 8 ]. To maintain pulsatile flow during total cardiopulmonary bypass, intra-aortic balloon pumping (IABP) can be used, but the insertion of the balloon is associated with additional surgical stress.…”