Effects of targeted mild hypercapnia versus normocapnia on cerebral oxygen saturation in patients undergoing laparoscopic hepatectomy under low central venous pressure: a prospective, randomized controlled study.

BACKGROUND: Laparoscopic hepatectomy under low central venous pressure (LCVP) is associated with intraoperative organ hypoperfusion, including cerebral hypoperfusion. We hypothesized that a ventilation strategy designed to achieve targeted mild hypercapnia (TMH) (end-tidal carbon dioxide partial pressure [PetCO2] of 45 ± 5 mmHg) rather than targeted normocapnia (TN) (PetCO2 of 30 ± 5 mmHg) would increase regional cerebral oxygen saturation (rSO2) during laparoscopic hepatectomy under LCVP. METHODS: Eighty patients undergoing laparoscopic hepatectomy under LCVP were randomly divided into the TMH group (n = 40) and the TN group (n = 40). Mechanical ventilation was adjusted to maintain the PetCO2 within the relevant range. Cerebral oxygenation was monitored continuously using the FORE-SIGHT system before anesthetic induction until the patient left the operating room. Patient and surgical characteristics, rSO2, intraoperative hemodynamic parameters (CVP, mean artery blood pressure [MAP], and heart rate), PetCO2, intraoperative blood gas analysis results, and postoperative complications were recorded. RESULTS: No significant differences were observed in CVP, MAP, and heart rate between the two groups during surgery. The rSO2 was significantly lower in the TN group on both the left and right sides during the intraoperative period (P < 0.05), while the TMH group had a stable rSO2. In the TN group, the mean rSO2 decreased most during liver parenchymal transection when compared with the baseline value (P < 0.05). The mean (standard deviation) percentage change in rSO2 from baseline to parenchymal transection was - 7.5% (4.8%) on the left and - 7.1% (4.6%) on the right. The two groups had a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings demonstrate that rSO2 is better maintained during laparoscopic hepatectomy under LCVP when patients are ventilated to a PetCO2 of 45 ± 5 mmHg (TMH) than a PetCO2 of 30 ± 5 mmHg (TN). TRIAL REGISTRATION: ChiCTR2100051130(14/9/2021).

Current Progress on Neuroinflammation-mediated Postoperative Cognitive Dysfunction: An Update.

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system (CNS) in elderly patients after surgery, showing cognitive changes such as decreased learning and memory ability, impaired concentration, and even personality changes and decreased social behavior ability in severe cases. POCD may appear days or weeks after surgery and persist or even evolve into Alzheimer's disease (AD), exerting a significant impact on patients' health. There are many risk factors for the occurrence of POCD, including age, surgical trauma, anesthesia, neurological diseases, etc. The level of circulating inflammatory markers increases with age, and elderly patients often have more risk factors for cardiovascular diseases, resulting in an increase in POCD incidence in elderly patients after stress responses such as surgical trauma and anesthesia. The current diagnostic rate of POCD is relatively low, which affects the prognosis and increases postoperative complications and mortality. The pathophysiological mechanism of POCD is still unclear, however, central nervous inflammation is thought to play a critical role in it. The current review summarizes the related studies on neuroinflammation-mediated POCD, such as the involvement of key central nervous cells such as microglia and astrocytes, proinflammatory cytokines such as TNF-α and IL-1ß, inflammatory signaling pathways such as PI3K/Akt/mTOR and NF-κB. In addition, multiple predictive and diagnostic biomarkers for POCD, the risk factors, and the positive effects of anti-inflammatory therapy in the prevention and treatment of POCD have also been reviewed. The exploration of POCD pathogenesis is helpful for its early diagnosis and long-term treatment, and the intervention strategies targeting central nervous inflammation of POCD are of great significance for the prevention and treatment of POCD.

Comparison of adjuvant pharmaceuticals for caudal block in pediatric lower abdominal and urological surgeries: A network meta-analysis.

STUDY OBJECTIVE: Caudal block helps relieve pain after sub-umbilical surgery in pediatric patients; however, the duration for which it exerts its analgesic effect is limited. The addition of certain adjuvant agents to local anesthetics (LAs) that are used to administer caudal block can prolong postoperative analgesia. Therefore, we aimed to compare the efficiencies and side effects of caudal adjuvants in the settings of pediatric lower abdominal and urological surgeries. DESIGN: A network meta-analysis (NMA). PATIENTS: One hundred and twelve randomized controlled trials (RCTs) involving 6800 pediatric patients were included in the final analysis. INTERVENTIONS: Different adjuvant agents, namely clonidine, dexamethasone, dexmedetomidine, fentanyl, ketamine, magnesium, midazolam, morphine, neostigmine, and tramadol. MEASUREMENTS: The primary outcome was the duration of analgesia. The secondary outcomes included the requirement for additional analgesia, analgesic consumption, and postoperative complications. The effects and rankings were evaluated using NMA and the surface under the cumulative ranking curve scores, respectively. RESULTS: Neostigmine, dexmedetomidine, and dexamethasone were found to be the three most effective adjuvants that prolong the duration of analgesia for caudal block, and these adjuvants extended this duration by 8.9 h (95% confidence interval [CI], 7.1-10.7), 7.3 h (95% CI, 6.0-8.6), and 5.9 h (95% CI, 4.0-7.7), respectively. Caudal neostigmine was associated with an increase in the incidence of postoperative nausea and vomiting, whereas dexmedetomidine and dexamethasone showed no postoperative complications. CONCLUSIONS: This NMA provided evidence and suggested that dexmedetomidine and dexamethasone may be the most beneficial adjuvant pharmaceutics adding to LAs for caudal block in children. However, given the off-label status of caudal dexmedetomidine and dexamethasone, further high-quality RCTs are still warranted, especially to determine whether delayed neurological complications will occur.

Postoperative analgesic effects of paravertebral block versus erector spinae plane block for thoracic and breast surgery: A meta-analysis.

BACKGROUND: Paravertebral block (PVB) is the most recognized regional anesthesia technique after thoracic epidural anesthesia for postoperative analgesia in thoracic and breast surgery. Erector spinae plane block (ESPB) is a recently discovered blocking technique, and it has evidenced excellent postoperative analgesia for breast and thoracic surgery with fewer adverse reactions. However, there are controversies about the postoperative analgesic effects of the two analgesic techniques. OBJECTIVE: To assess the analgesic effects of PVB versus ESPB in postoperative thoracic and breast surgery. METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to April 5, 2021. The primary outcome was postoperative pain scores. Secondary outcomes included: opioid consumption, additional analgesia, postoperative nausea and vomiting (PONV) 24 hours post-operation, and the time required for completing block procedure. This study was registered in PROSPERO, number CRD42021246160. RESULTS: After screening relevant, full-text articles, ten randomized controlled trials (RCTs) that met the inclusion criteria were retrieved for this meta-analysis. Six studies involved thoracic surgery patients, and four included breast surgery patients. Thoracic surgery studies included all of the outcomes involved in this meta-analysis while breast surgery did not report pain scores at movement and additional analgesia in 24 hours post-operation. For thoracic surgery, PVB resulted in significant reduction in the following pain scores: 0-1 hours (MD = -0.79, 95% CI: -1.54 to -0.03, P = 0.04), 4-6 hours (MD = -0.31, 95% CI: -0.57 to -0.05, P = 0.02), and 24 hours (MD = -0.42, 95% CI: -0.81 to -0.02, P = 0.04) at rest; significant reduction in pain scores at 4-6 hours (MD = -0.47, 95% CI: -0.93 to -0.01, P = 0.04), 8-12 hours (MD = -1.09, 95% CI: -2.13 to -0.04, P = 0.04), and 24 hours (MD = -0.31, 95% CI: -0.57 to -0.06, P = 0.01) at movement. Moreover, the opioid consumption at 24 hours post-operation (MD = -2.74, 95% CI: -5.41 to -0.07, P = 0.04) and the incidence of additional analgesia in 24 hours of the postoperative course (RR: 0.53, 95% CI: 0.29 to 0.97, P = 0.04) were significantly lower in the PVB group than in the ESPB group for thoracic surgery. However, no significant differences were found in pain scores at rest at various time points postoperatively, and opioid consumption at 24 hours post-operation for breast surgery. The time required for completing block procedure was longer in the PVB group than in the ESPB group for thoracic and breast surgery, and the incidence of PONV between the two groups showed no significant difference. CONCLUSION: The postoperative analgesic effects of PVB versus ESPB are distinguished by the surgical site. For thoracic surgery, the postoperative analgesic effect of PVB is better than that of ESPB. For breast surgery, the postoperative analgesic effects of PVB and ESPB are similar.

Propofol Affects EGF's Activity in Intestinal Cell by Down-Regulating EGFR-Mediated Intracellular Signaling.

Propofol is a commonly used anesthetic drug in clinic. In recent years, a series of non-anesthetic effects of propofol have been discovered. Studies have shown that propofol has many effects on the intestine. Epidermal growth factor (EGF) is one of the most important growth factors that could regulate intestinal growth and development. In the current study, we studied the effect of protocol on the biological activity of EGF on intestinal tissue and cell models. Through flow cytometry, indirect immunofluorescence and Western-blot and other technologies, it was found that propofol reduced the activity of EGF on intestinal cells, which inhibited EGF-induced intestinal cell proliferation and changed the cell behavior of EGF. To further explore the potential mechanism by which propofol down-regulated epidermal growth factor receptor (EGFR)-induced signaling, we carried out a series of related experiments, and found that propofol may inhibit the proliferation of intestinal cells by inhibiting the EGFR-mediated intracellular signaling pathway. The current research will lay the theoretical and experimental basis for further study of the effect of propofol on the intestine.

[Evaluation of the P-gp pump function on leukemic cell membrane and proper application of its reversal agents with Calcein-AM and flow cytometry].

OBJECTIVE: Leukemia is the most common malignancy in children. Combined chemotherapy is currently the primary treatment modality. During the past decade, very high cure rates of childhood acute lymphoblastic leukemia (ALL) have been reported both at home and abroad. However, the cure rates of children with acute myeloid leukemia (AML) remain low due to the multiple-drug resistance (MDR). P-glycoprotein (P-gp) is one of the most important mechanisms of MDR for leukemia cells. However, the function of the protein, the clinical application of its reversal agents and the efficacy of the combination of the reversal agents remain to be elucidated. The present study aimed to evaluate the P-gp pump function on leukemia cell membrane and the effects of the combined administration of the reversal agents cyclosporin A (CSA) and verapamil (VER) through the observation of Calcein-AM (C-AM) metabolism in the cell line K562 and its multi-drug resistant subline K562/VCR. METHODS: The mean fluorescence intensity (MFI) of C-AM inside the cytoplasm was analyzed with flow cytometry (FCM). The events of K562 and K562/VCR cells treated and untreated with CSA, VER and CSA + VER were acquired at time points 0, 30, 60, 90 and 120 minutes, respectively, and the data obtained were analyzed with CellQuest software. RESULTS: The C-AM in the K562 and K562/VCR varied more apparently in the fist 24 hours. In addition, the MFI of the C-AM in K562 was significantly higher than that in K562/VCR cells indicating that the P-gp pump molecules were functioning. The MFIs of the CSA, VER and CSA + VER groups co-cultured with K562/VCR cells were 4014 +/- 219, 3879 +/- 116 and 4158 +/- 302, respectively after 120 min of incubation, significantly higher as compared to that of control group (3251 +/- 107, P < 0.05). On the other hand, significant inhibition of the efflux from the K562/VCR cell line was also noticed after the same time period of incubation with the MFIs of 2237 +/- 155, 1932 +/- 233 and 2231 +/- 147, respectively in the three groups, which was significantly higher than that of control group (1622 +/- 191, P < 0.05). CSA, VER and CSA + VER could increase the uptake and inhibit the efflux of C-AM by K562/VCR cells, while no evident influence on those functions inside the parental cell line K562 cells was noticed. CONCLUSIONS: CSA, VER and CSA + VER could increase the uptake and reduce the efflux of C-AM by K562/VCR cells while no significant difference between the CSA + VER and CSA or VER was noticed. P-gp pump function and the effects of its reversal agents on leukemic cells can be rapidly and easily evaluated by using the C-AM and FCM.