Efficacy of bilateral catheter superficial parasternal intercostal plane blocks using programmed intermittent bolus for opioid-sparing postoperative analgesia in cardiac surgery with sternotomy: A randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: This study investigated whether catheter superficial parasternal intercostal plane (SPIP) blocks, using a programmed intermittent bolus (PIB) with ropivacaine, could reduce opioid consumption while delivering enhanced analgesia for a period exceeding 48 h following cardiac surgery involving sternotomy. DESIGN: A double-blind, prospective, randomized, placebo-controlled trial. SETTING: University-affiliated tertiary care hospital. PATIENTS: 60 patients aged 18 or older, scheduled for cardiac surgery via sternotomy. INTERVENTIONS: The patients were randomly assigned in a 1:1 ratio to either the ropivacaine or saline group. After surgery, patients received bilateral SPIP blocks for 48 h with 0.4% ropivacaine (20 mL per side) for induction, followed by bilateral SPIP catheters using PIB with 0.2% ropivacaine (8 mL/side, interspersed with a 2-h interval) or 0.9% normal saline following the same administration schedule. All patients were administered patient-controlled analgesia with hydromorphone. MEASUREMENTS: The primary outcome was the cumulative morphine equivalent consumption during the initial 48 h after the surgery. Secondary outcomes included postoperative pain assessment using the Numeric Rating Scale (NRS) at rest and during coughing at designated intervals for three days post-extubation. Furthermore, recovery indicators and ropivacaine plasma levels were diligently documented. MAIN RESULTS: Cumulative morphine consumption within 48 h in ropivacaine group decreased significantly compared to saline group (25.34 ± 31.1 mg vs 76.28 ± 77.2 mg, respectively; 95% CI, -81.9 to -20.0, P = 0.002). The ropivacaine group also reported lower NRS scores at all recorded time points (P < 0.05) and a lower incidence of nausea and vomiting than the saline group (3/29 vs 12/29, respectively; P = 0.007). Additionally, the ropivacaine group showed significant improvements in ambulation (P = 0.018), respiratory exercises (P = 0.006), and self-reported analgesia satisfaction compared to the saline group (P = 0.016). CONCLUSIONS: Bilateral catheter SPIP blocks using PIB with ropivacaine reduced opioid consumption over 48 h, concurrently delivering superior postoperative analgesia in adult cardiac surgery with sternotomy.

Preemptive deep parasternal intercostal plane block for perioperative analgesia in coronary artery bypass grafting with sternotomy: a randomized, observer-blind, controlled study.

OBJECTIVE: The precise characteristics of deep parasternal intercostal plane block (DPIP), which is useful for providing analgesia during open heart surgery, have not yet been thoroughly elucidated. In this study, we aimed to establish the efficacy, define the cutaneous sensory block area, and determine the duration of preemptive DPIP block at the T3-4 or T4-5 intercostal spaces in patients undergoing coronary artery bypass grafting (CABG) via sternotomy. DESIGN: A prospective, single-blind, randomized controlled trial. SETTING: Patients were randomly divided into three cohorts, each containing thirty patients. PARTICIPANTS: Ninety patients who underwent elective CABG via sternotomy were included in this study. INTERVENTIONS: The T3-4 and T4-5 groups received a preoperative single-shot DPIP block at the respective intercostal spaces. The principal objective of the study was to ascertain the optimal dosage of sufentanil administered during surgical procedures involving either a DPIP block or its absence, and to conduct a comparative analysis thereof across distinct injection sites, specifically T3-4 and T4-5. Secondary factors considered were the dosage of postoperative analgesics, the extent of sensory block on the skin, pain levels after extubation, time of recovery from anesthesia (time to extubation), duration of the block, and the occurrence of nausea and vomiting. MEASUREMENTS & MAIN RESULTS: Preemptive DPIP block significantly reduced intraoperative sufentanil requirement compared to the control group (T3-4:0.38 ± 0.1, T4-5:0.32 ± 0.10, vs. Control:0.88 ± 0.3 µg/kg/h, p < 0.001). It also resulted in decreased analgesic consumption and numeric rating scale scores on the day of surgery (p < 0.01 compared to the control group). The DPIP block provided accurate anesthetic coverage of the dermatomes in the sternal region and reduced the time to extubation and postoperative nausea. However, the injection point (either via the T3-4 intercostal or the T4-5 intercostal) did not affect the efficacy. Preoperative DPIP block failed to provide adequate analgesia beyond 24 h post-surgery. CONCLUSION: Preemptive bilateral DPIP block provided effective analgesia in patients undergoing CABG during surgery and in the early postoperative period. The analgesic effects of the DPIP block in the T3-4 and T4-5 intercostal spaces were comparable.

BET Bromodomain Suppression Inhibits VEGF-induced Angiogenesis and Vascular Permeability by Blocking VEGFR2-mediated Activation of PAK1 and eNOS.

The tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) is a critical modulator of angiogenesis. Increasing evidence indicate the important role of bromodomain and extra-terminal domain (BET) of chromatin adaptors in regulating tumor growth and inflammatory response. However, whether BET proteins have a role in angiogenesis and endothelial permeability is unclear. In this study, we observed that treatment with JQ1, a specific BET inhibitor, suppressed in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis in a Matrigel plug and oxygen-induced retinopathy neovascularization. JQ1 attenuated the VEGF-induced decrease in TEER in HUVECs and prevented Evans blue dye leakage in the VEGF-induced Miles assay in athymic Balb/c nude mice. BET inhibition with JQ1 or shRNA for Brd2 or Brd4 suppressed VEGF-induced migration, proliferation, and stress fiber formation of HUVECs. Furthermore, BET inhibition suppressed phosphorylation of VEGFR2 and PAK1, as well as eNOS activation in VEGF-stimulated HUVECs. Inhibition with VEGFR2 and PAK1 also reduced migration and proliferation, and attenuated the VEGF-induced decrease in TEER. Thus, our observations suggest the important role of BET bromodomain in regulating VEGF-induced angiogenesis. Strategies that target the BET bromodomain may provide a new therapeutic approach for angiogenesis-related diseases.