Acute Cytokine Response During Breast Cancer Surgery: Potential Role of Dexamethasone and Lidocaine and Relationship with Postoperative Pain and Complications - Analysis of Three Pooled Pilot Randomized Controlled Trials

Purpose: An imbalance in perioperative cytokine response may cause acute pain and postoperative complications. Anesthetic drugs modulate this cytokine response, but their role in non-major breast cancer surgery is unclear. In an exploratory study, we investigated whether intravenous lidocaine and dexamethasone could modulate the cytokine response into an anti-inflammatory direction. We also evaluated interrelationships between cytokine levels, pain scores and postoperative complications. Our goal is to develop multimodal analgesia regimens optimizing outcome after breast cancer surgery. Patients and Methods: Forty-eight patients undergoing a lumpectomy were randomly assigned to placebo or lidocaine (1.5 mg⋅kg-1 followed by 2 mg⋅kg-1⋅hour-1) supplemented by dexamethasone zero, 4 or 8 mg, yielding six groups of eight patients. Interleukin (IL)-1β, IL-1Ra, IL-6, IL-10 levels and pain scores were measured at baseline and four hours postoperatively. We assessed postoperative complications occurring within 30 days. We noted persistent pain and infections as potential immune-related complications (PIRC). We used multiple regression to disentangle the effects of the individual study drugs (given by their partial regression coefficients (b)). Odds ratios (OR) estimated the link between pain scores and complications. Results: Dexamethasone 8 mg increased IL-10 (b=12.70 (95% CI=8.06-17.34), P<0.001). Dexamethasone 4 mg and 8 mg decreased the ratio IL-6/IL-10 (b=-2.60 (-3.93 to -1.26), P<0.001 and b=-3.59 (-5.04 to -2.13), P