April 17, 2012

Pathways to delirium in the ICU

Study suggests that the “kynurenine” biochemical pathway could be a target for reducing delirium and coma in critically ill patients.


Delirium – incoherence of thought and inattention – in intensive care unit (ICU) patients is associated with increased length of hospital stay, mortality and long-term cognitive impairment. Despite its high prevalence, the pathophysiology is unclear.

Pratik Pandharipande, M.D., Jessica Adams Wilson, M.D., and colleagues previously demonstrated that plasma tryptophan levels were associated with delirium in ICU patients. Tryptophan – a precursor for the neurotransmitter serotonin – can be metabolized through an alternate kynurenine pathway, and an imbalance in beneficial and neurotoxic kynurenine metabolites was hypothesized to be associated with delirium. The investigators studied plasma kynurenine and tryptophan levels in 84 ICU patients. They report in the March issue of Critical Care Medicine that elevated plasma kynurenine and kynurenine/tryptophan ratios were both associated with fewer days free of delirium/coma, after adjusting for sedative exposure, age and severity of illness.

The findings demonstrate that increased kynurenine pathway activation is associated with longer duration of acute brain dysfunction. The kynurenine pathway could be a therapeutic target for reducing delirium/coma in ICU patients.

This research was supported by the National Institute on Aging of the National Institutes of Health, by the Veterans Affairs Clinical Science Research and Development Service, and by the Veterans Affairs Tennessee Valley Geriatric Research, Education and Clinical Center.