Blood Test May Help Predict Confusion Post-Surgery

Many people experience an extended period of confusion when they awake after surgery and this acute confusional state, called delirium, particularly affects older adults and poses an important clinical challenge as it can lead to greater postoperative complications and may extend hospitalization.

Several biological models of delirium have been proposed and these include neuroinflammation, neurological aging, neuroendocrine stress, neurotransmitter dysregulation, oxidative stress, sleep/wake dysregulation, and network disconnectivity. The identification of a marker associated with delirium would advance our understanding of the pathophysiology of delirium and ultimately lead to new interventions that could improve patient outcomes.


Medial scientists at the Beth Israel Deaconess Medical Center enrolled 566 patients equal to or greater than 70 years old who were scheduled for major non-cardiac surgery, including total hip or knee replacement, cervical or lumbar laminectomy, abdominal aortic aneurysm repair, lower extremity vascular bypass, or colectomy. Patients received either general or spinal anesthesia. Blood samples were drawn at four time points before and after surgery from relatively healthy older adults who were undergoing major elective surgery.

The initial proteomics phase used isobaric tags for relative and absolute quantitation mass spectrometry assay to examine five sets of matched case-control plasma samples across the four time points in the discovery cohort. Relative quantitation proteomics was performed using the iTRAQ isobaric tagging system. In the biomarker validation stage, an antibody-based enzyme-linked immunosorbent assay (ELISA) was employed.

The scientists used a global proteomics approach to compare all proteins in the blood from a subset of the patients, C-reactive protein (CRP) emerged with the strongest association to postoperative delirium. In a discovery cohort of 39 matched cases, control pairs revealed that cases had higher CRP levels before the surgery and two days after, when delirium peaks. In a replication cohort of 36 different matched pairs, cases had higher CRP levels immediately after surgery and two days later.

Sarinnapha Vasunilashorn, PhD, co-first author of the study, said, “Our ability to pinpoint CRP levels as being significantly elevated before and after postoperative delirium onset establishes CRP as a risk marker, as well as a disease marker, for delirium. The findings also provide insight into what causes delirium and what puts someone at risk.” The study was published on January 15, 2017, in the journal Biological Psychiatry.