Intraoperative Flurbiprofen Treatment Alters Immune Checkpoint Expression in Patients Undergoing Elective Thoracoscopic Resection of Lung Cancer.

OBJECTIVES: This study aimed to determine the effect of intraoperative administration of flurbiprofen on postoperative levels of programmed death 1 (PD-1) in patients undergoing thoracoscopic surgery. MATERIALS AND METHODS: In this prospective double-blind trial, patients were randomized to receive intralipid (control group, n = 34, 0.1 mL/kg, i.v.) or flurbiprofen axetil (flurbiprofen group, n = 34, 50 mg, i.v.) before induction of anesthesia. PD-1 levels on T cell subsets, inflammation, and immune markers in peripheral blood were examined before the induction of anesthesia (T0) and 24 h (T1), 72 h (T2), and 1 week (T3) after surgery. A linear mixed model was used to determine whether the changes from baseline values (T0) between groups were significantly different. RESULTS: The increases in the percentage of PD-1(+)CD8(+) T cells observed at T1 and T2 in the control group were higher than those in the flurbiprofen group (T1: 12.91 ± 1.65 vs. 7.86 ± 5.71%, p = 0.031; T2: 11.54 ± 1.54 vs. 8.75 ± 1.73%, p = 0.004), whereas no differences were observed in the changes in the percentage of PD-1(+)CD4(+) T cells at T1 and T2 between the groups. Moreover, extensive changes in the percentage of lymphocyte subsets and inflammatory marker concentrations were observed at T1 and T2 after surgery and flurbiprofen attenuated most of these changes. CONCLUSIONS: Perioperative administration of flurbiprofen attenuated the postoperative increase in PD-1 levels on CD8(+) T cells up to 72 h after surgery, but not after this duration. The clinical relevance of changes in PD-1 levels to long-term surgical outcome remains unknown.

Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation.

While effective treatments for acute respiratory distress syndrome (ARDS) are lacking, mechanical lung ventilation can sustain adequate gas exchange in critically ill patients with respiratory failure due to ARDS. However, as a result of the phenomenon of ventilator-induced lung injury (VILI), there is an increasing need to seek beneficial pharmacological therapies for ARDS. Recent studies have suggested the renin-angiotensin system (RAS), which consists of the ACE/Ang-II/AT1R axis and ACE2/Ang-(1-7)/MasR axis, plays a dual role in the pathogenesis of ARDS and VILI. This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.

Operation, Effectiveness, and Limitations of Continuous Serratus Anterior Plane Blocks for Thoracoscopic Surgery in Adults.

PURPOSE: This randomized, double-blind study evaluated the effectiveness and limitations of continuous serratus anterior plane block (cSAPB) by comparing the effect of cSAPB to patient-controlled intravenous analgesia (PCIA) on postoperative acute pain after thoracoscopic surgery in adults. PATIENTS AND METHODS: Sixty-six patients who underwent elective video-assisted thoracoscopic surgery (VATS) were randomly allocated to cSAPB or PCIA groups (n=33 per group) after surgery. For the cSAPB group, patients were treated by an initial does of 20 mL ropivacaine (0.375%), followed by continuous infusion at a rate of 5 mL/h of ropivacaine (0.2%) and a patient-controlled bolus of 5 mL ropivacaine (0.2%). PCIA started with an initial does of 0.03 µg/kg sufentanil, followed by a basal infusion of 0.03 µg/kg/h sufentanil and a patient-controlled bolus of 0.03 µg/kg sufentanil. Visual analog scale (VAS) and other items were examined postoperatively. The area under the curve of VAS-time (AUCVAS-time) at rest and on coughing in the first 24 hours postoperatively were primary outcomes. RESULTS: At the first 24 hours postoperatively, patients in the cSAPB group exhibited a smaller AUCVAS-time at rest (44.0±17.1 vs 68.9±11.8 cm·h, P<0.001) and AUCVAS-time on coughing (67.1±8.8 vs 78.0±12.5 cm·h, P<0.001) compared with those in the PCIA group. The differences in means of VAS score at rest were more than 1.0 cm between the two groups, however, on coughing they were less than 1.0 cm at each observation point. Additionally, patients in the cSAPB group had a longer time to first patient-controlled bolus (15.8±7.6 vs 10.6±8.6 hours, P=0.011). Furthermore, a higher rank of satisfaction was recorded with patients in the cSAPB group. CONCLUSION: cSAPB using PCA devices might be superior to traditional intravenous continuous analgesia, particularly with an advantage of pain relief at rest following VATS operation. Meanwhile, cSAPB lacks a satisfactory analgesic effect on cough.

Goal-directed fluid restriction using stroke volume variation and cardiac index during one-lung ventilation: a randomized controlled trial.

BACKGROUND: Goal-directed therapy confers a strong prognosis in patients undergoing major cardiac or noncardiac surgery. The present study investigated whether intraoperative goal-directed fluid restriction (GDFR) using stroke volume variation (SVV) and cardiac index could improve oxygenation and postoperative outcome in patients undergoing one-lung ventilation (OLV). METHODS: A Total of 168 patients scheduled for elective thoracoscopic lobectomy under OLV were randomized into the GDFR protocol (group G) or conventional fluid therapy groups (group C). Patients in group C underwent conventional fluid therapy based on mean arterial pressure (MAP), central venous pressure (CVP), and urine volume, whereas those in group G received GDFR protocol associated with the SVV from 10-13% and the cardiac index was controlled at a minimum of 2.5 L/min/m2. The primary outcome variable was PaO2/FiO2. The secondary outcomes were other pulmonary variables and lung mechanics, inflammatory response, the incidence of postoperative pulmonary complications, and the length of hospital stay. RESULTS: During surgery, the PaO2/FiO2 ratio in group G was more than that of group C at 30 and 60 min after OLV, 10 min after re-expansion, and the end of the operation (259±29 vs. 314±34; 253±30 vs. 308±35; 341±34 vs. 394±39; 349±35 vs. 401±39, respectively, all P<0.001). Compared to conventional fluid therapy, GDFR protocol also significantly improved the hemodynamic and lung mechanics with the initiation of OLV. The incidence of postoperative pulmonary complications such as acute lung injury and pneumonia, and the length of hospital stay were decreased by GDFR protocol as compared to conventional fluid therapy (all P<0.05). However, there were no significant differences between groups with respect to the concentration of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10). CONCLUSIONS: The GDFR protocol based on SVV and cardiac index applied in patients undergoing OLV improves intraoperative pulmonary oxygenation. It can also reduce the postoperative complications and length of hospital stay. However, the GDFR strategy cannot reduce the local or systemic inflammation. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR-INR-16008288, Registered 20 April, 2016.

A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery.

The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-ß levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients.