Blood Analyses Predict Delirium Risk In Older Surgical Patients

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 and has been linked with longer hospital stays, greater postoperative complications, and higher rates of discharge to nursing homes.

In the USA health care costs attributable to delirium are upwards of USD164 billion annually, yet there are no established biological markers to guide the diagnosis or management of the condition. Recent studies may now help clinicians assess an individual patient's risk of developing post-operative delirium, enabling preventive measures to safeguard their health.


Scientists at the Beth Israel Deaconess Medical Center (Boston, MA, USA) and their colleagues 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% experienced delirium. Plasma was collected at four time points: preoperatively (PREOP), in the post anesthesia care unit (PACU), on postoperative day two (POD2) and at the one-month follow-up appointment (PO1MO).

Cases and controls were matched on six variables that may influence the relationship between C-reactive protein (CRP) and postoperative delirium: age within five years; baseline general cognitive performance (GCP) within five points; and an exact match for sex, surgery type, presence of vascular comorbidity, and apolipoprotein E (APOE) ε4 carrier status. For APOE genotyping, DNA was extracted from cellular material collected at PREOP and analyzed.

The initial proteomics phase used isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry assay to examine five sets of matched case-control plasma samples across the four time points in the discovery cohort. Mass spectrometry data was obtained using the AB Sciex 4800 MALDI-TOF/TOF instrument (AB Sciex, Framingham, MA, USA). After analyzing five matched pairs using the iTRAQ system, they selected one protein that met two criteria for enzyme-linked immunosorbent assay (ELISA) validation. ELISA plates were read using a Synergy plate reader (BioTek Instruments, Winooski, VT, USA) at Optical Density (OD =450nm).

C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the PREOP median paired difference [MPD] was 1.97 mg/L, 0.29 mg/L, 1.56 mg/L, the PACU MPD was 2.83 mg/L, 2.22 mg/L, 2.53 mg/L) and the POD2 MPD was 71.97 mg/L, 35.18 mg/L,63.76 mg/L time points, but not at one month postoperative.

Towia A. Libermann, PhD, a senior author of the study said, “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. We anticipate that the most specific delirium biomarkers will be found at very low concentrations and not among the most common proteins.” The study was published on March 25, 2016, in the journal Biological Psychiatry.

Related Links:
Beth Israel Deaconess Medical Center
AB Sciex
BioTek Instruments