A clinical perspective of sepsis-associated delirium

Abstract

The term sepsis-associated encephalopathy (SAE) has been applied to animal models, postmortem studies in patients, and severe cases of sepsis. SAE is considered to include all types of brain dysfunction, including delirium, coma, seizure, and focal neurological signs. Clinical data for sepsis-associated delirium (SAD) have been accumulating since the establishment of definitions of coma or delirium and the introduction of validated screening tools. Some preliminary studies have examined the etiology of SAD. Neuroinflammation, abnormal cerebral perfusion, and neurotransmitter imbalances are the main mechanisms underlying the development of SAD. However, there are still no specific diagnostic blood, electrophysiological, or imaging tests or treatments specific for SAD. The duration of delirium in intensive care patients is associated with long-term functional disability and cognitive impairment, although this syndrome usually reverses after the successful treatment of sepsis. Once the respiratory and hemodynamic states are stabilized, patients with severe sepsis or septic shock should receive rehabilitation as soon as possible because early initiation of rehabilitation can reduce the duration of delirium. We expect to see further pathophysiological data and the development of novel treatments for SAD now that reliable and consistent definitions of SAD have been established.

Keywords: Acute brain dysfunction; Coma; Confusion Assessment Method for the Intensive Care Unit (CAM-ICU); Delirium; Intensive Care Delirium Screening Checklist (ICDSC); Sepsis-associated encephalopathy (SAE).

Fig. 1

Illustration of acute brain dysfunction (coma and delirium). The sun represents the investigator. The sunbeam represents the interview or tests (i.e., CAM-ICU) used to assess inattention. The clouds (i.e., RASS score of ≤−4) represent cover on some levels of arousal required to maintain cognition. RASS −3 the patient opens their eyes or moves in response to a voice but does not make eye contact. RASS −1 the patient is not fully alert but opens their eyes and makes eye contact, which is sustained for more than 10 s in response to a voice

Fig. 2

The relationships between coma and delirium in contrast to acute respiratory distress syndrome

Fig. 3

The mechanism of sepsis-associated delirium. Double-lined boxes correspond to the clinical evidence reported in the main text. SIRS systemic inflammatory response syndrome, ROS reactive oxygen species, NO nitric oxide

Fig. 4

Diagnostic decision tree for acute brain dysfunction and sepsis-associated delirium (SAD). RASS Richmond Agitation–Sedation Scale, EEG electroencephalogram, SEP sensory evoked potential, CT computed tomography, MRI magnetic resonance imaging