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Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study
Dillon ST, Vasunilashorn SM, Ngo L, Otu HH, Inouye SK, Jones RN, Alsop DC, Kuchel GA et al.. Biological psychiatry, 2016-03-25
Topic: Brain proteins, microglia and lab models
Background Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation. Methods The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation-based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium. Results 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 preoperative (median paired difference [MPD] 1.97 mg/L [p < .05], 0.29 mg/L, 1.56 mg/L [p < .01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p < .05], 2.53 mg/L [p < .01]) and postoperative day 2 (MPD 71.97 mg/L [p < .01], 35.18 mg/L [p < .05], 63.76 mg/L [p < .01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, -0.66 mg/L, 1.10 mg/L). Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.
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APA 7th
Dillon, S. T., Vasunilashorn, S. M., Ngo, L., Otu, H. H., Inouye, S. K., Jones, R. N., et al. (2017). Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study. Biological psychiatry. https://doi.org/10.1016/j.biopsych.2016.03.2098
Vancouver
Dillon ST, Vasunilashorn SM, Ngo L, Otu HH, Inouye SK, Jones RN, et al. Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study. Biological psychiatry. 2017. doi:10.1016/j.biopsych.2016.03.2098. PMID: 27160518.
BibTeX
@article{dillon2017-27160518,
author = {Dillon, S. T. and Vasunilashorn, S. M. and Ngo, L. and Otu, H. H. and Inouye, S. K. and Jones, R. N. and Alsop, D. C. and Kuchel, G. A. and others},
title = {{Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study}},
journal = {Biological psychiatry},
year = {2017},
doi = {10.1016/j.biopsych.2016.03.2098},
pmid = {27160518},
url = {https://doi.org/10.1016/j.biopsych.2016.03.2098}
}
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Key findings
- Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium.
- Results 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 preoperative (median paired difference [MPD] 1.97 mg/L [p < .05], 0.29 mg/L, 1.56 mg/L [p < .01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p < .05], 2.53 mg/L [p < .01]) and postoperative day 2 (MPD 71.97 mg/L [p < .01], 35.18 mg/L [p < .05], 63.76 mg/L [p < .01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, -0.66 mg/L, 1.10 mg/L).
- Conclusions Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.
Study details
- Study designcase-control study
- Participants566
- Evidence strengthModerate
How this study scored 60/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 35 of the 58 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biological psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 566 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27160518) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
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