Markers may help identify patients who would
benefit from preventive measures against delirium
Newswise, May 12, 2016 – Delirium, or sudden severe confusion
due to rapid changes in brain function that can occur with physical or mental
illness, affects 15% to 53% of older surgical patients.
New research led by investigators at Beth Israel Deaconess Medical
Center (BIDMC) may now help clinicians assess an individual patient’s risk of
developing post-operative delirium, enabling preventive measures to safeguard their
health.
Published online in the journal Biological Psychiatry, the
research also provides insights into the potential mechanisms involved in the
development of delirium, which could lead to new therapeutic strategies.
Delirium in older surgical patients has been linked with
longer hospital stays, greater postoperative complications, and higher rates of
discharge to nursing homes.
In the United States, health care costs attributable to
delirium are upwards of $164 billion annually, yet there are no established
biological markers to guide the diagnosis or management of the condition.
To look for potential blood-based markers of delirium, a team
led by senior investigators Towia Libermann, PhD and Edward Marcantonio, MD,
SM, both of BIDMC, screened plasma from adults without dementia aged 70 and
older undergoing major non-cardiac surgery using data from the Successful Aging
after Elective Surgery Study.
Of the 566 patients enrolled, 24 percent experienced delirium.
Plasma was collected at four time points: preoperatively (PREOP), in the
postanesthesia care unit (PACU), on postoperative day 2 (POD2) and at a 1-month
follow-up appointment (PO1MO).
High levels of a protein called C-reactive protein (CRP),
which has been linked to inflammation and infection, emerged from an analysis
of more than 100 proteins as being strongly linked to delirium.
Compared with patients without delirium, those with delirium
had significantly higher plasma CRP levels at PREOP, PACU, and POD2, but not at
PO1MO.
Although the relationship between CRP and delirium has been
previously reported, this study is the first to document and analyze CRP levels
before onset of symptoms.
“Our findings demonstrate that, in patients who go on to
develop delirium, CRP levels in blood are slightly increased before surgery and
further increase after surgery relative to patients who do not develop
delirium,” said Libermann, who is Director of the Genomics, Proteomics,
Bioinformatics and Systems Biology Center at BIDMC and Associate Professor of
Medicine at Harvard Medical School (HMS).
Further, he noted that increased plasma CRP levels are linked
to various clinical conditions, which means that CRP is not a highly specific
marker for delirium. To identify more selective delirium markers, the
investigators are planning to expand their search to include metabolites,
lipids and less abundant proteins in the blood.
“We anticipate that the most specific delirium biomarkers will
be found at very low concentrations and not among the most common proteins,”
Libermann explained.
Uncovering such markers may provide clues regarding the
mechanisms that underlie the development of delirium.
“We speculate that, despite the heterogeneity of patients and
delirium, common mechanisms are shared by all patients developing postoperative
delirium and that a pre-inflammatory state as reflected by slightly increased
levels of CRP even before surgery predisposes patients to a more pronounced
inflammatory response upon surgery that increases the likelihood of delirium,”
said Libermann.
“From a clinical standpoint, our findings suggest that CRP
could be used to risk stratify patients before surgery, enabling proactive
interventions that target patients at risk for developing postoperative
delirium,” said Sarinnapha Vasunilashorn, PhD, co-lead author and postdoctoral
fellow in the Division of General Medicine at Primary Care at BIDMC and HMS.
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