Cerebral hemodynamics in sepsis assessed by transcranial Doppler: a systematic review and meta-analysis

Abstract

Cerebral microcirculation is gradually compromised during sepsis, with significant reductions in the function of capillaries and blood perfusion in small vessels. Transcranial Doppler ultrasound (TCD) has been used to assess cerebral circulation in a typical clinical setting. This study was to systematically review TCD studies, assess their methodological quality, and identify trends that can be associated with the temporal evolution of sepsis and its clinical outcome. A meta-analysis of systematic reviews was conducted according to the PRISMA statement. Articles were searched from 1982 until the conclusion of this review in December 2015. Twelve prospective and observational studies were selected. Evaluations of cerebral blood flow, cerebral autoregulation, and carbon dioxide (CO) vasoreactivity were summarized. A temporal pattern of the evolution of the illness was found. In early sepsis, the median blood flow velocity (Vm) and pulsatility index (PI) increased, and the cerebral autoregulation (CA) remained unchanged. In contrast, Vm normalization, PI reduction and CA impairment were found in later sepsis (patients with severe sepsis or septic shock). Cerebral haemodynamic is impaired in sepsis. Modifications in cerebral blood flow may be consequence to the endothelial dysfunction of the microvasculature induced by the release of inflammatory mediators. A better understanding of cerebral hemodynamics may improve the clinical management of patients with sepsis and, consequently, improve clinical outcomes.

Impact of fluid challenge increase in cardiac output on the relationship between systemic and cerebral hemodynamics in severe sepsis compared to brain injury and controls

“…The baseline higher CO and lower MAP in the sepsis group in our study was associated with a higher PSV, but with an EDV not different than the control group. These observations are consistent with previous studies that demonstrated an increase in MCAv and pulsatile index during the early phase of sepsis [ 10 , 26 , 29 , 35 , 36 ]. The FC-induced CO increase in the sepsis group of our study was associated with an increased systolic and diastolic BP in some patients and an increased PSV and EDV.…”

“…Blood pressures remained relatively stable in these studies, and CBF changes secondary to CO changes might result from changes in cerebrovascular resistance. However, the mechanisms responsible for the change in CBF related to changes in CO remain speculative [ 9 , 10 ]. The present study did not find any relationship between CO changes and MCAv changes in control patients under sedation.…”

“…The cerebral specificity for this tuning of vascular tone allows the maintenance of CBF adaptation to metabolic demand with relative independence from systemic hemodynamic changes and their regulatory factors [ 1 – 3 ]. The paucity of data available on the relationship between systemic blood flow (cardiac output CO and stroke volume SV) and CBF in humans [ 4 – 8 ], particularly in presence of systemic inflammation [ 9 , 10 ] or brain injury [ 11 – 14 ], had motivated this study. The actual debate on fluid resuscitation for patients with acute systemic inflammation associated not with vasopressors is poorly focused on regional blood flow.…”

Impaired cerebral autoregulation is associated with brain dysfunction in patients with sepsis

“…Thus, in our cohort CAR is impaired, regardless of the PaCO 2 level. In a recent meta-analysis, there was no clear association between PaCO 2 and/or CO 2 reactivity with impaired CAR during sepsis [ 33 ]. As such, future studies prospectively evaluating the effects of changes in CO 2 and CAR function are warranted.…”

Antioxidant Melatonin: Potential Functions in Improving Cerebral Autoregulation After Subarachnoid Hemorrhage

“…The structural and functional integrity of endothelial cells is essential for maintaining stable cerebral autoregulation ( Preckel et al, 1996 ; White et al, 2000 ; Ainslie et al, 2007 ; Guo et al, 2016 ). After SAH, both structural and functional integrity were damaged because of factors, such as the high concentration of ROS/RNS and inflammatory responses ( Figure 1 ) ( Kajita et al, 1998 ; Scharbrodt et al, 2009 ; Szatmari et al, 2010 ; Sabri et al, 2011 ; Qin et al, 2012 ; Liu et al, 2016 ; de Azevedo et al, 2017 ; Shekhar et al, 2017 ; Armstead et al, 2018 ). In inflammatory responses, various inflammatory pathways, such as the NF-κB pathway ( Pawlowska et al, 2018 ), NLRP3 pathway ( Li et al, 2016 ; Shao et al, 2016 ), and TLR4 pathway ( Zhang et al, 2016 ), are activated and have negative effects on the arterial endothelium after SAH.…”