The spectrum of sepsis-associated encephalopathy: a clinical perspective

Abstract

Sepsis-associated encephalopathy is a severe neurologic syndrome characterized by a diffuse dysfunction of the brain caused by sepsis. This review provides a concise overview of diagnostic tools and management strategies for SAE at the acute phase and in the long term. Early recognition and diagnosis of SAE are crucial for effective management. Because neurologic evaluation can be confounded by several factors in the intensive care unit setting, a multimodal approach is warranted for diagnosis and management. Diagnostic tools commonly employed include clinical evaluation, metabolic tests, electroencephalography, and neuroimaging in selected cases. The usefulness of blood biomarkers of brain injury for diagnosis remains limited. Clinical evaluation involves assessing the patient's mental status, motor responses, brainstem reflexes, and presence of abnormal movements. Electroencephalography can rule out non-convulsive seizures and help detect several patterns of various severity such as generalized slowing, epileptiform discharges, and triphasic waves. In patients with acute encephalopathy, the diagnostic value of non-contrast computed tomography is limited. In septic patients with persistent encephalopathy, seizures, and/or focal signs, magnetic resonance imaging detects brain injury in more than 50% of cases, mainly cerebrovascular complications, and white matter changes. Timely identification and treatment of the underlying infection are paramount, along with effective control of systemic factors that may contribute to secondary brain injury. Upon admission to the ICU, maintaining appropriate levels of oxygenation, blood pressure, and metabolic balance is crucial. Throughout the ICU stay, it is important to be mindful of the potential neurotoxic effects associated with specific medications like midazolam and cefepime, and to closely monitor patients for non-convulsive seizures. The potential efficacy of targeted neurocritical care during the acute phase in optimizing patient outcomes deserves to be further investigated. Sepsis-associated encephalopathy may lead to permanent neurologic sequelae. Seizures occurring in the acute phase increase the susceptibility to long-term epilepsy. Extended ICU stays and the presence of sepsis-associated encephalopathy are linked to functional disability and neuropsychological sequelae, underscoring the necessity for long-term surveillance in the comprehensive care of septic patients.

Keywords: Coma; Delirium; Encephalopathy; Prognosis; Seizures; Sepsis.

Fig. 1

Aspect, prevalence, and prognostic value of EEG patterns in sepsis-associated encephalopathy. (Prevalence and prognosis data from Azabou et al. [31], Berisavac et al. [32], Gilmore et al. [36], Hosokawa et al. [30], Benghanem et al. [37], Velissaris et al. [28]). ^⊥These EEG patterns observed without concomitant sedation were associated with mortality. Definitions: Background frequency is described as δ (0.2–3.5 Hz), θ (4–7.5 Hz), α (8–13 Hz) or β (14–30 Hz) bands. Low voltage (200ms). Sporadic triphasic waves: rare slow wave with an initial negative deflection (upward) followed by a positive component (downward) and then negative again; when associated to encephalopathy, they are ample diffuse slow waves, frequently prominent in the fronto-central regions. Periodic discharges: abundant periodic abnormalities (spike or wave, with a return to the EEG background between abnormalities), during >50% of the recording. Rhythmic discharges: abundant rhythmic discharges (spike or wave, without return to the EEG background between abnormalities) during >50% of the recording. Electrographic seizure: rhythmic discharges at >2.5 Hz for ≥10 seconds or any pattern with definite spatio-temporal evolution and lasting ≥10 seconds

Fig. 2

A simplified algorithm for the diagnosis of sepsis-associated encephalopathy. CSF cerebrospinal fluid; EEG Electroencephalography; ICU Intensive Care Unit; TSH thyroid-stimulating hormone

Fig. 3

A multimodal approach for the management of sepsis-associated encephalopathy. EEG Electroencephalography; SAE Sepsis-Associated Encephalopathy

Fig. 4

Complications associated with sepsis-associated encephalopathy at the acute phase and in the long term