Septic encephalopathy

Reviewed and revised 3 January 2016


  • Septic encephalopathy is brain dysfunction mediated by the septic inflammatory response, independent of other co-existent causes such as liver or renal dysfunction
  • up to 70% of patients with sepsis have some degree of encephalopathy
  • sometimes  known as sepsis-induced or sepsis-associated delirium
  • a degree of long-lasting cognitive impairment is common following recovery from sepsis


  • requires recognition of brain dysfunction in the setting of sepsis, through clinical, biochemical or electrophysiological methods
  • no universally agreed diagnostic criteria
  • in practice the detection of delirium using tools such as CAM-ICU in patients with sepsis is a pragmatic approach
  • EEG is more sensitive that clinical criteria alone
  • Brain imaging (MRI/CT) may show non-specific findings such as cerebral infarction, leukoencephalopathy, and vascular edema
  • Biochemical markers (e.g. S100 beta and neuron-specific enolase or NSE) have not been shown to be reliable and have clinical role at present


The mechanisms underlying septic encephalopathy are poorly understood.

Proposed mechanisms involve:

  • oxidative stress
  • cytokines and pro-inflammatory factors
  • altered blood brain barrier permeability
  • altered levels of CSF and serum amino acids
  • endothelial dysfunction
  • changes in cerebral circulation
  • emboli of microvessels

Leading to:

  • altered synthesis and secretion of neurotransmitters
  • degeneration of neurons in various areas of the nervous system


  • hyperactive or hypoactive delirium
  • often manifests before the onset of other organ dysfunction
    • this can be clinically important, sub-clinical encephalopathy may be identified by family members as the patient being “not quite right” even thought abnormalities are not obvious to the bedside clinician
  • may progress to coma
  • other features such as anorexia, malaise, myoclonus and asterixis may be present
  • seizures (general or focal) uncommonly occur


  • no specific therapy exists
  • manage delirium, seizure and coma
  • seek and treat underlying cause and complications of sepsis


  • 45% of sepsis survivors have cognitive impairment at 1 year
  • cognitive impairment may persist for years
  • up to 58% of sepsis survivors have long-term symptoms of depression and/or anxiety
  • delirium is associated with increased mortality in ICU patients

References and links


Journal articles

  • Ebersoldt M, Sharshar T, Annane D. Sepsis-associated delirium. Intensive care medicine. 33(6):941-50. 2007. [pubmed]
  • Flierl MA, Rittirsch D, Huber-Lang MS, Stahel PF. Pathophysiology of septic encephalopathy–an unsolved puzzle. Critical care. 14(3):165. 2010. [pubmed] [free full text]
  • Ziaja M. Septic encephalopathy. Current neurology and neuroscience reports. 13(10):383. 2013. [pubmed] [free full text]

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.