Perioperative Medicine  |   December 2015
Patient-specific Immune States before Surgery Are Strong Correlates of Surgical Recovery
Author Notes
  • From the Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, California (G.K.F., B.G., N.A., G.P.N.); Department of Microbiology and Immunology, Stanford University, Stanford, California (G.K.F., G.P.N.); and Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, California (B.G., E.A.G., M.T., M.S.A.).
  • This article is featured in “This Month in Anesthesiology,” page 3A.
    This article is featured in “This Month in Anesthesiology,” page 3A.×
  • Corresponding article on page 1221.
    Corresponding article on page 1221.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • The first two and last two authors contributed equally to this work (G.K.F., B.G., G.P.N., and M.S.A.).
    The first two and last two authors contributed equally to this work (G.K.F., B.G., G.P.N., and M.S.A.).×
  • Submitted for publication February 8, 2015. Accepted for publication June 4, 2015.
    Submitted for publication February 8, 2015. Accepted for publication June 4, 2015.×
  • Address correspondence to Dr. Angst: Department of Anesthesia, Stanford University School of Medicine, Office S276, Grant Building, 300 Pasteur Drive, Stanford, California 94305. ang@stanford.edu. This article may be accessed for personal use at no charge through the Journal Web site, www.anesthesiology.org.
Article Information
Perioperative Medicine / Clinical Science / Pain Medicine / Quality Improvement
Perioperative Medicine   |   December 2015
Patient-specific Immune States before Surgery Are Strong Correlates of Surgical Recovery
Anesthesiology 12 2015, Vol.123, 1241-1255. doi:10.1097/ALN.0000000000000887
Anesthesiology 12 2015, Vol.123, 1241-1255. doi:10.1097/ALN.0000000000000887
Abstract

Background: Recovery after surgery is highly variable. Risk-stratifying patients based on their predicted recovery profile will afford individualized perioperative management strategies. Recently, application of mass cytometry in patients undergoing hip arthroplasty revealed strong immune correlates of surgical recovery in blood samples collected shortly after surgery. However, the ability to interrogate a patient’s immune state before surgery and predict recovery is highly desirable in perioperative medicine.

Methods: To evaluate a patient’s presurgical immune state, cell-type–specific intracellular signaling responses to ex vivo ligands (lipopolysaccharide, interleukin [IL]-6, IL-10, and IL-2/granulocyte macrophage colony-stimulating factor) were quantified by mass cytometry in presurgical blood samples. Selected ligands modulate signaling processes perturbed by surgery. Twenty-three cell surface and 11 intracellular markers were used for the phenotypic and functional characterization of major immune cell subsets. Evoked immune responses were regressed against patient-centered outcomes, contributing to protracted recovery including functional impairment, postoperative pain, and fatigue.

Results: Evoked signaling responses varied significantly and defined patient-specific presurgical immune states. Eighteen signaling responses correlated significantly with surgical recovery parameters (|R| = 0.37 to 0.70; false discovery rate < 0.01). Signaling responses downstream of the toll-like receptor 4 in cluster of differentiation (CD) 14+ monocytes were particularly strong correlates, accounting for 50% of observed variance. Immune correlates identified in presurgical blood samples mirrored correlates identified in postsurgical blood samples.

Conclusions: Convergent findings in pre- and postsurgical analyses provide validation of reported immune correlates and suggest a critical role of the toll-like receptor 4 signaling pathway in monocytes for the clinical recovery process. The comprehensive assessment of patients’ preoperative immune state is promising for predicting important recovery parameters and may lead to clinical tests using standard flow cytometry.

Abstract

In an analysis of the same group of orthopedic surgery patients from the postoperative sample study, preoperative immune state as assessed by mass cytometry of blood samples was predictive of recovery across several domains, with toll-like receptor 4 signaling in cluster of differentiation 14+ monocytes accounted for 50% of observed variance.

Supplemental Digital Content is available in the text.