JAMA NEUROLOGY | MAY 01, 2018

Evered L, Silbert B, Scott DA, Zetterberg H and Blennow K.

JAMA Neurol. 2018;75(5):542-547

DOI: 10.1001/jamaneurol.2017.4913

This study was peformed using a Simoa® Homebrew assay.

ABSTRACT

Key Points

Question:  Do anesthesia and surgery lead to changes in levels of neurofilament light and tau, 2 biomarkers of neurological injury now detectable in blood?

Findings: In this study, mean plasma neurofilament light increased postoperatively to a maximal increase at 48 hours. Tau levels also increased significantly from baseline with a peak increase at 6 hour postoperatively, after which they declined but still remained elevated for at least 48 hours.

Meaning:  These findings indicate that general anesthesia and surgery exert neurotoxicity on the central nervous system, which has implications for both neurological outcomes and for the mechanism of anesthesia.

Abstract

Importance:  Anesthesia and surgery are believed to act on the central nervous system by a fully reversible mechanism innocuous to nerve cells. Evidence that neurological sequelae may follow would challenge this belief and would thereby suggest a need to reassess theories of the mechanism of anesthetic action or the response of the central nervous system to surgery.

Objective:  To measure 2 biomarkers of neurological injury (neurofilament light and tau) in plasma in a series of timed collections before and after anesthesia and surgery.

Design, Setting, and Participants:  These 2 related observational studies (CAPACITY and ARCADIAN) recruited patients 60 years and older who were undergoing general anesthesia for surgeries performed within a tertiary hospital. Blood samples were taken immediately before surgical anesthesia was administered and then sequentially after surgery at 30-minute, 6-hour, 24-hour, and 48-hour intervals. Sampling took place from January 2014 to August 2015. Data analysis took place from October 2016 to February 2017.

Main Outcomes and Measures:  Plasma neurofilament light and tau.

Results:  A total of 30 patients were enrolled (13 from the CAPACITY study and 17 from the ARCADIAN study). The mean (SD) age was 69.1 (7.0) years, and 18 members (59%) of the participant group were female; 22 (73%) were undergoing joint arthroplasty. Mean neurofilament light increased at each measurement from a combined baseline mean (SD) of 22.3 (20.4) pg/mL to a maximal combined mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 67% (95% CI, 45%-89%; P < .001), at 48 hours postoperatively. The level of tau increased significantly from baseline at every measurement, from a combined baseline mean (SD) of 3.1 (1.3) pg/mL to a maximal combined mean (SD) of 10.8 (9.5) pg/mL, a peak increase of 257% (95% CI, 154%-361%; P < .001), at 6 hours postoperatively. After 6 hours, the mean level began to return to baseline but remained elevated after 48 hours.

Conclusions and Relevance:  Neurofilament light is a specific marker of axonal injury and has been shown to indicate neuronal damage in a number of diseases. Tau proteins are an integral component of axonal integrity, and increased tau indicates neuronal damage. The increases in both neurofilament light and tau over 48 hours after surgery suggest that general anesthesia and surgery may be associated with neuronal damage in the short term. Further investigations will be required to study any association with clinical outcomes. These preliminary findings demand that we question the prevailing assumption that anesthesia and surgery are innocuous, transient, and without injurious changes to the central nervous system.