General Versus Regional Anesthesia in Orthopedic Surgery: Effects on Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Systemic Immune-Inflammation Index: A Systematic Review with Narrative Synthesis

Abstract

Background: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and the newer systemic immune-inflammation index (SII = neutrophil × platelet / lymphocyte count) and systemic inflammation response index (SIRI = neutrophil × monocyte / lymphocyte count) are inexpensive, complete-blood-count-derived indices increasingly used to characterize the perioperative inflammatory response and to predict complications such as delirium, infection, and mortality in orthopedic patients. Anesthetic technique general anesthesia (GA) versus regional anesthesia (spinal, neuraxial, or peripheral nerve block, PNB) is a modifiable perioperative exposure that may independently shape these indices, separately from surgical trauma itself, and has already been studied extensively for its effect on hard clinical outcomes in orthopedic surgery.

Methods: MEDLINE/PubMed and general academic web search (search-engine mediated; institutional access to Embase, Scopus, Web of Science, and Cochrane CENTRAL was not available for this review) were searched for studies in adult patients undergoing orthopedic surgery that directly compared GA against a regional anesthesia technique and reported at least one of NLR, PLR, or SII/SIRI as a perioperative outcome. Risk of bias was assessed with Cochrane RoB 2 for the included randomized trial and the Newcastle-Ottawa Scale for the included retrospective/cohort studies. Given cross-study heterogeneity, biomarker findings were synthesized narratively rather than by pooled meta-analysis.

Results: Four studies met inclusion criteria for the biomarker synthesis, spanning upper-limb fracture/forearm surgery and total knee arthroplasty (TKA). Regional anesthesia was associated with a smaller postoperative rise in NLR in 2 of 3 studies reporting it, and with lower PLR in 1 of 3 studies reporting it. One large retrospective TKA cohort found anesthesia type to be an independent predictor of the change in SII, favoring spinal anesthesia. Risk-of-bias assessment found the included RCT at some concern (chiefly unclear allocation concealment) and the three retrospective cohorts at moderate-to-good quality on the Newcastle-Ottawa Scale, with confounding by indication (anesthesia type was not randomized in three of four studies) as the principal shared limitation. Mechanistic evidence from total hip arthroplasty, shoulder surgery, and older cytokine-based TKA studies is broadly consistent with an anti-inflammatory effect of regional anesthesia, though generally modest and often not statistically significant. This biomarker-level signal contrasts somewhat with the larger randomized and registry literature on anesthetic technique in orthopedic surgery, which has found little or no difference in hard outcomes such as postoperative delirium or 60-day mortality between spinal and general anesthesia in hip fracture surgery.

Conclusions: Active and recent evidence base suggests regional anesthesia may attenuate the postoperative rise in NLR and, in large cohort, SII, relative to general anesthesia in orthopedic surgery, without any study reporting the reverse. This biomarker-level signal is a laboratory finding, an established clinical benefit larger trials addressing hard outcomes have reached more conclusions.