The Effect Of Perioperative Lidocaine On Lymphocyte’s Function And Release Of HMGB1in Patients Undergoing Radical Hysterectomy And Pelvic Lymphadenectomy

Background:Surgery and trauma can enhance the body’s hypothalamic-pituitary-adrenal axis (HPA) of endocrine system, enhance the responses of sympathetic nervous system and the acute phase of the stress response. It can trigger the body’s stress-induced inflammatory response or even systemic inflammatory response syndrome, accompanied by activation of the immune system with processing and releasing of high levels of proinflammatory mediators, leading to rapid suppression of the body’s immune function. The immunosuppressive effects caused by surgical stress is an important cause of postoperative infection and acceleration of the residual tumor’s metastasis. As a commonly used amides local anesthetic, lidocaine not only has the analgesic, anti-hyperalgesia, anti-arrhythmic effect, but also has been shown to have the anti-inflammatory effects. Studies have shown that perioperative intravenous lidocaine can reduce postoperative pain, reduce the amount of opioid analgesic drug use and accelerate the recovery of gastrointestinal function and shortened the length of hospital stay. High mobility group protein B1(HMGB1) is expressed abnormally high in a variety of malignant tumors. As a late inflammatory protein, studies have shown that it mediates the body’s inflammatory response to infection and injury, thereby promoting the occurrence and development of inflammatory reactions. In this study, by observing the effects of perioperative continuous infusion of lidocaine on lymphocyte’s proliferation, apoptosis, Thl/Th2drift and release of HMGB1in patients undergoing radical hysterectomy and pelvic lymphadenectomy, we discuss lidocaine’s protective effects and its mechanism on immune function destroyed by surgery trauma, hoping to provide a theoretical basis for lidocaine being used in clinical anti-inflammatory treatment.Methods:Thirty cervical cancer patients scheduled for radical hysterectomy (radical hysterectomy and pelvic lymph node dissection) under general anesthesia in Shandong University Qilu Hospital between June2013and January2014were recruited to this randomized, placebo-controlled study. All the patients signed the informed consent to participate in this study. Patients were randomly divided into two groups, the control group(C) and the lidocaine group(L). Both patients and anesthesiologists were blind. There were no statistical differences in clinical baseline between the two groups. Fifteen patients in the treatment group received intravenous lidocaine (1.5mg/kg bolus) starting15mins before induction of general anesthesia (bolus lasted approximately10mins), followed by a1.5mg/kg/h infusion until the end of the surgical procedure, whereas the control group (15patients) received a matched saline infusion. Venous blood samples (10ml) were collected24h before surgery, at the end of the surgery and48h after surgery. Centrifugate, collect the plasma and isolate peripheral lymphocytes. Apoptosis detection test and PHA-induced proliferation assay of isolated lymphocytes were determined by Annexin V/PI assay and CCK-8respectively. Cytokine production of Interferon (IFN)-y, Interleukin(IL)-4and HMGB1were examined by enzyme-linked immune-sorbent assay (ELISA).Results:1、 There were no statistical differences between the two groups in age, weight and other clinical baseline before surgery(p>0.05).2、 Compared with group C, in group L, PHA induced lymphocyte proliferation activity Oh after the surgery (0.448±0.139vs.0.352±0.112OD) and48h after the surgery (0.420±0.094vs.0.326±0.141OD) was lower(p<0.05).3、 Lymphocyte’s apoptosis detection test by Annexin V/PI assay showed that both the two group’s apoptosis rate increased after the surgery.48h after the surgery, compared with group C, the apoptosis rate was higher (3.560±0.775vs.4.173±0.779%, p<0.05).4、48h after the surgery, compared with group C, the concentration of IFN-y increased (4.041±0.230vs.3.782±0.282pg/ml,p<0.05); the ratio of IFN-y/IL-4in plasma was calculated for both groups,48h after the surgery, the ratio of group L was higher than that of the group C (0.676±0.288vs.0.489±0.124,p<0.05).5、48h after the surgery, compared with group C, the concentration of HMGB1in group L was lower(53.458±8.983vs.59.387±5.025μg/L,p<0.05).Conclusions:1、Perioperative intravenous lidocaine can improve the proliferative ability of lymphocytes damaged by surgery trauma.2、Perioperative intravenous lidocaine can reduce the apoptosis of lymphocytes.3、Perioperative intravenous lidocaine can change the balance of Thl/Th2and protect the immune function.4、The modulatory effect of perioperative intravenous lidocaine on body’s immune function may be releated to lidocaine’s down regulatory effect of the expression of HMGB1.Significance:Our study observed the effect of perioperative intravenous lidocaine on body’s immune function. On the one hand, we proved the anti-inflammatory effects of lidocaine again and provided a theoretical basis for lidocaine’s clinical applications. On the other hand, we suggested that the modulatory effect of perioperative intravenous lidocaine on body’s immune function may be releated to lidocaine’s down regulatory effect of the expression of HMGB1. It provided a new way for clinical anti-inflammatory treatment, but the exact mechanism of this hypothesis was not yet clear, still need to be further studied.