Open liver surgery remains a primary surgical approach for complex liver resections and liver transplantation. However, the postoperative pain management is still a major challenge. Ultrasound-guided external oblique intercostal (EOI) plane block is a novel approach of regional anaesthesia and has a great potential to relieve postoperative pain after upper abdominal surgeries. This study aims to investigate the efficacy and safety of ultrasound-guided EOI plane block in managing postoperative pain after open liver surgery. Seventy-four participants scheduled for open liver surgery will be randomly assigned to either the intervention group, receiving an ultrasound-guided EOI plane block with a single dose of 30 ml 0.375% ropivacaine, or the control group, which will not receive this block. All participants will be provided with opioid-based patient-controlled intravenous analgesia (PCIA) postoperatively. The primary outcome is resting pain score at 3 h postoperatively, assessed using numerical rating scale. Secondary outcomes include pain score at 6, 24, 48, and 72 h postoperatively, perioperative opioid consumption, remedial analgesics within 72 h postoperatively, PCIA usage within postoperative 72 h, postoperative recovery, length of hospital stay, postoperative side effects, block-related complications, and ropivacaine plasma concentration of participants receiving the block. This study is a randomised controlled trial to evaluate the efficacy and safety of ultrasound-guided EOI plane block for postoperative analgesia after open liver surgery. As regional anaesthesia plays an important role in the multimodal pain management, EOI plane block may prove to be an effective regional technique for enhancing postoperative pain relief and contributing to enhanced recovery after open liver surgery. Chinese Clinical Trial Registry ChiCTR2200065745. Registered on November 14, 2022.

Background/Objectives: The external oblique intercostal (EOI) plane block shows promise for postoperative analgesia after open liver surgery. Pharmacokinetic profiles of ropivacaine after EOI plane block remain unclear. Meanwhile the pharmacokinetic data informs safety assessment, guides post-block monitoring duration, and predicts blockade duration. This study aimed to characterize ropivacaine pharmacokinetics and propose a safe dosing regimen. Methods: In this prospective study, patients undergoing open liver surgery received a unilateral single-shot ultrasound-guided EOI plane block with 30 mL of 0.375% ropivacaine. Plasma ropivacaine concentrations were measured to define pharmacokinetics, identify influencing factors, and develop physiology-based pharmacokinetic (PBPK) models for dose optimization. Results: Twenty-eight patients (Child-Pugh A, ≤3 liver segments resected) were included. Peak plasma ropivacaine concentration occurred at 10 min and remained below the toxic threshold in all patients. No adverse events were observed. Demographic and surgical factors did not significantly affect pharmacokinetics. The PBPK model-predicted safe doses of ropivacaine were comparable across age groups and relatively high. Conclusions: A single-shot EOI plane block with ropivacaine is safe for patients undergoing open liver surgery (Child-Pugh A) with limited resection (≤3 segments). This study provides critical pharmacokinetic data and validated PBPK model, guiding safe dosing to reduce toxicity risks.

Dexmedetomidine (DEX) exhibits notable sedative, analgesic, and anesthetic-sparing properties. While growing evidence suggests these effects are linked to the modulation of γ-aminobutyric acid (GABA) system, the precise pre- and postsynaptic mechanisms of DEX action on cortical GABAergic signaling remain unclear. In this study, we applied whole-cell patch-clamp recording to investigate the impact of DEX on GABAergic transmission in layer 5 pyramidal neurons of the mouse primary somatosensory cortex. We recorded spontaneous inhibitory postsynaptic currents (sIPSCs), miniature IPSCs (mIPSCs), and evoked inhibitory postsynaptic potentials (eIPSPs) before and during DEX application. Our findings demonstrated that DEX reduced activity-dependent spontaneous GABAergic transmission, as evidenced by a decrease in sIPSC frequency, while mIPSC frequency was unaffected. eIPSPs were not significantly influenced by DEX either. Additionally, DEX prolonged the kinetics of both sIPSCs and mIPSCs, increasing the rise and decay times of sIPSCs and the decay time of mIPSCs. We proposed that DEX modulated cortical neuronal activity by limiting GABA release and altering GABA_A receptor kinetics. Collectively, these results indicated that DEX modulated cortical GABAergic signaling at both presynaptic and postsynaptic sites, which likely underlined its sedative, analgesic, and anesthetic-sparing effects.

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

Background: Optimizing intravascular volume (IV) before surgery is crucial for patients undergoing resection of functioning pheochromocytomas and paragangliomas (PPGLs). While point-of-care ultrasound (POCU) is a noninvasive technique to assess IV, the use of POCU to evaluate preoperative IV and its relationship to perioperative adverse outcomes (PAOs) remains largely unexplored. Methods: We conducted a prospective cohort study including patients who underwent PPGL resection following preoperative α-blockade. Preoperative IV was assessed using inferior vena cava (IVC) ultrasound and clinical parameters. We used logistic regression models to examine the associations between preoperative IV and intraoperative hemodynamic instability (IHI), perioperative organ dysfunction (POD), and PAO. We also compared the predicting abilities of IVC ultrasound measurements and clinical parameters for PAOs. Results: A total of 80 patients were recruited and analyzed. The study population carried a heavy comorbidity burden (median age-adjusted Charlson Comorbidity Index 4), thus the median duration of preoperative α-blockade was 60 (30, 98) days. Based on IVC ultrasound, 27 patients were classified as having appropriate volume status and 53 as inappropriate volume status. We found no significant association between IVC ultrasound assessed IV status and IHI, POD, and PAO. Furthermore, neither IVC ultrasound assessments nor clinical parameters could discriminate PAOs, and the predictive performance of the two methods did not differ significantly. However, this finding should be interpreted with caution, as the study was likely to be underpowered (enrolled 80 of 364 planned patients, 22%). Conclusion: In this study with a sample size of 80 patients, no independent association was found between preoperative IVC ultrasound measurements and PAOs in patients undergoing PPGL resection with an extended duration of preoperative α-blockade preparation [60 (30, 98) days]. The utility of point-of-care IVC ultrasound in guiding preoperative volume optimization for these patients merits further exploration.