Cerebral Perfusion in Sepsis

Abstract

IntroductionSepsis, the host's reaction to infection, characteristically includes multi-organ dysfunction. Brain dysfunction is often one of the fi rst clinical symptoms in sepsis and may manifest as sepsis-associated delirium in up to 70% of patients [1,2], less often as focal defi cits or seizures [3]. As severely reduced global perfusion leading to hypotension, maldistribution of regional blood fl ow, and tissue hypoperfusion is a key feature of severe sepsis and septic shock, the question whether there is a link between cerebral perfusion and brain dysfunction in sepsis is obvious. However, clinical and experimental data on cerebral perfusion in sepsis are often inconsistent and most reports only include small numbers of animals or patients. We summarize the current literature on the eff ects of the infl ammatory response on cerebral per fusion and review the eff ects of altered cerebral perfusion on brain function in sepsis. Sepsis and the brainIn sepsis, the brain may be aff ected by many systemic disturbances, such as hypotension, hypoxemia, hyperglycemia, hypoglycemia, and organ dysfunction (e.g., increased levels of ammonia in liver dysfunction or urea in acute kidney injury). Direct brain pathologies, such as ischemic brain lesions, cerebral micro-and macrohemorrhage, microthrombi, microabscesses, and multifocal necrotizing leukencephalopathy, have also been described in histopathologic examinations [4,5]. However, in addition to these metabolic and `mechanical' eff ects on the brain, infl ammation by itself causes profound alterations in cerebral homeostasis in sepsis. Infl ammation and the brainSepsis at the outset causes a hyperinfl ammatory reaction, followed by a counteractive anti-infl ammatory reaction. Pro-and anti-infl ammatory cytokines are initially upregu lated. Despite its anatomical sequestration from the immune system by the blood-brain barrier, the lack of a lymphatic system, and a low expression of histocompatibility complex antigens, the brain is not isolated from the infl ammatory processes occurring elsewhere in the body. Th e circumventricular organs lack a bloodbrain barrier, and through these specifi c brain regions blood-borne cytokines enter the brain [5,6]. Th e circumventricular organs are composed of specialized tissue and are located in the midline ventricular system. Th ey consist of the organum vas culosum, the pineal body, the subcommissural organ, and the subfornical organ. Th ey also express components of the immune system (Toll-like receptors [TLR]), and receptors for cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α).A further mechanism by which the brain can detect systemic infl ammation is through aff erent vagal fi bers ending in the nucleus tractus solitarius, which senses visceral infl ammation through its axonal cytokine receptors. In response to the detection of systemic infl ammation, behavioral, neuroendocrine, and autonomic responses are generated including expression of immune receptors and cytokines, induci...

Association between sepsis and dementia

“…Some studies found that the inflammatory response to sepsis might increase permeability of the blood-brain barrier and affect cerebral blood flow and cerebral perfusion. These disturbances in patients with sepsis could contribute to brain dysfunction or injury [22,23].…”

Cerebral vasoreactivity to acetazolamide is not impaired in patients with severe sepsis

“…In a recent review summarizing the present knowledge, Burkhart et al [4] explained these differences in vasoreactivity tests by small sample sizes, differences in the timing of the measurements, and the different degrees of severity of the septic patients included in the studies.…”

“…It is believed that microcirculatory alterations, disturbances of cerebral autoregulation, and flow-metabolism coupling mechanisms may also play a role [2][3][4].…”

Gas Diffusion in the CNS

“…NO is produced in large quantities by iNOS during systemic inflammation and gives rise to nitrosylation of proteins, which, in turn, can stimulate contraction of smooth muscle cells of cerebral arteries (Elliott et al, ). NO production–driven peroxynitrite may therefore underlie sepsis‐associated cerebral hypoperfusion and dysfunction (Burkhart et al, ; Berg et al, ). However, even though mice genetically deficient in iNOS do display less long‐term behavioral and cognitive sequelae after systemic administration of a high dose of bacterial lipopolysaccharides than wild‐type mice, both strains display comparable cortical glucose utilization (Weberpals et al, ).…”