• Citer

Alteration of cerebral perfusion as a cause of cerebral complications associated with sepsis

par Ferlini, Lorenzo
Président du jury Lybaert, Pascale
Promoteur Gaspard, Nicolas
Co-Promoteur Taccone, Fabio
Publication Non publié, 2023-03-09

Thèse de doctorat

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

Sepsis-induced impairment of cerebral function is the result of the interaction of multiples factors.The findings of our studies show that the alteration in perfusion potentially plays a role in SAE dueto a disruption of the mechanisms of CBF regulation that negatively influence cortical function. Thealteration of these protective mechanisms is a dynamic process. We showed that CA becomesimpaired only in the late phases of sepsis and this in odds with previous literature. Therefore, in aclinical scenario, patients frequently present a shifted CA curve, due to other medical preexistingconditions, preventing a correct interpretation of CA parameters. Since methods to monitor CA inreal time are increasingly available, prospective randomized trials should be underwent to answer thequestion of whether individualizing perfusion pressure targets in septic patients has a positive effectover outcome. Some studies suggested that NVC might be less robust against a sepsis-inducedinflammation challenge. Accordingly, we showed that, already in early phases of sepsis, NVCbecomes less performant to sustain the seizure-induced increase in neuronal activity. Furthermore, inhealthy animals, recurring seizure might independently alter the control mechanisms of cerebralperfusion which become inadequate to balance the enormous metabolic needs of rapidly firingneurons resulting in a reduction in inter-ictal tissue oxygenation. Thus, the association of seizure andsepsis may be particularly dangerous in those patients presenting a prior condition known to alterNVC (such as subarachnoid haemorrhage, traumatic brain injury or ischemic stroke). We showed inour animal model that systemic inflammation does not trigger spontaneous seizures in a healthy brain.This finding was confirmed by clinical data of our highly selected patient cohort, since we do notrecord any spontaneous seizure. Sepsis won’t be a risk factor for seizure occurrence per se but,reducing seizure threshold, it may elicit them in a predisposed brain (i.e. in patients presenting witha pre-existing brain pathology). In septic patients, PDs are associated with unfavorable functionaloutcome and mortality and they might contribute to SAE development, independently from sedation.The amount and duration of PDs, the so-called burden, equally correlated with outcome. This findingsuggests that the recurrence of these epileptiform abnormalities might challenge an already weakenedNVC leading to brain hypoxia and secondary brain injury. Although speculative, this hypothesis issupported by the reduction in tissue oxygenation that we recorded in case of recurring seizures andby previous studies that showed, in condition of NVC alteration, that PDs had a similar effect ondetected only with EEG which also provides useful informatiobrain tissue O2 and metabolic balance than seizures. Since epileptiform abnormalities can be detected only with EEG which also provides useful information to diagnosis SAE, continuous EEGshould be included among basic tools for brain monitoring in septic patients. Randomized trialsshould address the question of whether the treatment of PDs may improve clinical outcome in septicpatients.