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Intensive Care Medicine
Published in: Intensive Care Medicine 8/2004

01-08-2004 | Original

Antibiotic-mediated release of tumour necrosis factor alpha and norharman in patients with hospital-acquired pneumonia and septic encephalopathy

Authors: Verena Eggers, Katja Fügener, Ortrud Vargas Hein, Hans Rommelspacher, Melvyn P. Heyes, Wolfgang J. Kox, Claudia D. Spies

Published in: Intensive Care Medicine | Issue 8/2004

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Abstract

Objective

To investigate antibiotic-mediated release of tumour necrosis factor (TNF)-α and norharman in patients with hospital-acquired pneumonia with and without additional septic encephalopathy.

Design

Prospective observational study with a retrospective post hoc analysis.

Setting

Surgical intensive care unit (ICU) at a university hospital.

Patients

Thirty-seven patients were consecutively included (9 patients with hospital-acquired pneumonia, 11 patients with hospital-acquired pneumonia and septic encephalopathy, 17 control patients) in the study. Pneumonia was defined according to the criteria of the American Thoracic Society.

Interventions

Patients received cephalosporins for antibiotic treatment of hospital-acquired pneumonia. Blood samples were taken before, immediately after and 4 h after application of cephalosporins.

Measurements and results

Of the pneumonia patients, 55% developed septic encephalopathy. ICU stay, complications and mortality were significantly increased. An increased release of TNF-α was immediately seen in all pneumonia patients after antibiotics compared to controls, whereas the level did not differ between patients with and without septic encephalopathy. Norharman was significantly increased in pneumonia patients 4 h after antibiotic treatment, in tendency more enhanced in the pneumonia patients without encephalopathy.

Conclusions

Patients with hospital-acquired pneumonia and septic encephalopathy had a significantly longer ICU stay with higher mortality rate compared to patients with hospital-acquired pneumonia alone. Antibiotic-mediated TNF-α release may induce the kynurenine pathway. TNF-α activates indolamine-2,3-dioxygenase with neurotoxic quinolinic acid as the end product. Norharman seems to counteract this mechanism and seems to play a role in neuroprotection. The worse outcome of patients with encephalopathy expresses the need to investigate protective factors and mechanisms.
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Metadata
Title
Antibiotic-mediated release of tumour necrosis factor alpha and norharman in patients with hospital-acquired pneumonia and septic encephalopathy
Authors
Verena Eggers
Katja Fügener
Ortrud Vargas Hein
Hans Rommelspacher
Melvyn P. Heyes
Wolfgang J. Kox
Claudia D. Spies
Publication date
01-08-2004
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 8/2004
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-004-2285-6

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