Associations of inflammatory biomarkers with morbidity and mortality after noncardiac surgery: A systematic review and meta-analysis

Abstract

Background

Noncardiac surgery is associated with an inflammatory response. Whether increased inflammation in the perioperative period is associated with subsequent morbidity and mortality is unknown.

Methods

MEDLINE, EMBASE, and CENTRAL were systematically searched from date of inception until May 2023. Longitudinal studies were included if they reported multivariable adjusted associations of biomarkers measured preoperatively and/or within 10 days after surgery with at least one prespecified adverse outcome in noncardiac surgery patients. Data were extracted independently and in duplicate. Risk estimates were pooled using DerSimonian-Laird random-effects models and reported as summary odds ratios (ORs) with 95% CIs. The outcomes were all-cause mortality and major adverse cardiovascular events.

Results

Fifty-two studies with a total of 121,849 patients were included. The median follow-up was 56 [IQR, 28–63] months and the average age was 57 (±3) years. Elevated preoperative C-reactive protein (CRP) levels were associated with a higher risk of mortality (OR 1.57, 95% CI 1.29–1.90, I² = 93%, 28 studies). This association was stronger in non-cancer surgery populations (OR 2.10, 95% CI 1.92–2.31, I² = 0%, 4 studies) when compared to cancer surgery populations (OR 1.51, 95% CI 1.26–1.81, I² = 83%, 24 studies) (p for subgroup difference = 0.001). Similarly, higher postoperative CRP levels were associated with all-cause mortality (OR 1.61, 95% CI 1.17–2.20, I² = 90%, 7 studies). Higher preoperative CRP levels were associated with major cardiovascular events (OR 2.11, 95% CI 1.51–2.94, I² = 0%, 2 studies). Other preoperatively measured biomarkers associated with all-cause mortality were fibrinogen (OR 1.48, 95% CI 1.05–2.09, I² = 52%, 5 studies), interleukin-6 (OR 1.17, 95% CI 1.07–1.28, I² = 27%, 3 studies), and tumour necrosis factor-alpha (OR 1.37, 95% CI 1.16–1.61, I² = 0%, 2 studies).

Conclusion and relevance

Inflammatory biomarker levels in the perioperative period were associated with all-cause mortality and adverse cardiovascular events in patients undergoing noncardiac surgery.