Treatment of septic encephalopathy and encephalitis – a critical appraisal

ABSTRACT

Introduction

The central nervous system is frequently involved during severe sepsis. Patients either develop septic encephalopathy characterized by delirium and coma or focal neurological signs as a consequence of septic-embolic or septic-metastatic encephalitis.

Areas covered

In this review, a summary of currently available literature on established and some promising experimental treatment options for septic encephalopathy and encephalitis is provided, with a focus on the clinical utility of published studies.

Expert opinion

Treatment relies on proper identification of the causative pathogen and rapidly initiated adequate empirical or (after identification of the pathogen) tailored antibiotic therapy, fluid and electrolyte management. In the presence of brain abscess(es) or mycotic aneurysm(s), surgery or interventional neuroradiology must be considered. Pharmacological approaches to prevent delirium of different etiology include the use of dexmedetomidine and (with limitations) of melatonin and its derivatives. In the absence of a specific pharmacological treatment, non-pharmacological bundles of interventions (e.g. promotion of sleep, cognitive stimulation, early mobilization and adequate therapy of pain) are of proven efficacy to prevent delirium of different etiology including sepsis. Experimental promising therapies include the use of non-bacteriolytic antibiotics and the reduction of the toxic effects of microglial activation.

KEYWORDS:

• Septic encephalopathy
• septic-embolic encephalitis
• septic-metastatic encephalitis
• brain abscess
• mycotic aneurysm
• antibiotics
• pexidartinib (PLX3397)

Acknowledgement

We thank Omid Nikoubashman, Dept. of Neuroradiology, RWTH University Hospital Aachen, for kindly providing the cranial radiological and magnetic resonance images.

Article highlights

• A hierarchy for the treatment of central nervous system (CNS) complications of sepsis is essential to properly care for these patients in critical clinical conditions.

• The backbone is proper identification of the causative pathogen and rapidly initiated adequate empirical or (after identification of the pathogen) tailored antibiotic therapy, fluid and electrolyte management.

• In the presence of brain abscess(es) or mycotic aneurysm(s), surgery or interventional neuroradiology must be considered.

• Pharmacological approaches to prevent delirium of different etiology in intensive care unit settings include the use of dexmedetomidine and (with limitations) of melatonin and its derivatives.

• Non-pharmacological bundles of interventions are of proven efficacy to prevent delirium of different etiology including sepsis.

• The bundle of interventions most effective is the combination of promotion of the circadian rhythm including restful sleep at night, cognitive stimulation, early mobilization and adequate control of pain.

• Promising approaches for future therapy in septic encephalopathy are non-bacteriolytic bactericidal antibiotics aiming at a reduction of pro-inflammatory bacterial products and inhibition of the toxic effects of microglial activation.

• Sepsis and septic encephalopathy, in part, can be prevented by rigorous vaccinations and probably the long-term use of statins (HMG-CoA-reductase inhibitors) in all patients with an established cardiovascular indication.

Declaration of interest

SC Tauber has served on the scientific advisory boards of Roche and Merck & Co and has received travel and speaker honoraria from Novartis, Teva, Merck & Co, Roche and Biogen. R Nau has received travel and speaker’s honoraria from Bayer Vital, Pfizer, Bristol-Myers Squibb, Novartis, Otto-Loewi-Stiftung, and Tillotts Pharma as well as research support from Novartis, Braun Melsungen, Strathmann, Tillotts Pharma, the German Society for Geriatrics, and Innovationsausschuss. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by the German Society for Geriatrics.