Daily Anesthesiology Research Analysis

BACKGROUND: Opioids such as morphine are essential for the management of moderate to severe pain. However, their prolonged use leads to tolerance. Although the central mechanisms of morphine tolerance have been extensively studied, the peripheral molecular pathways remain poorly understood. METHODS: We performed time-course RNA sequencing of the dorsal root ganglia (DRG) from a morphine tolerance mouse model, followed by mechanistic studies using genetic and pharmacological manipulations combined with behavioural, molecular, and biochemical assays. RESULTS: Acute morphine administration reduced Mas-related G protein-coupled receptor D (Mrgprd) expression in DRG neurones by ∼70% within 6-24 hours, with levels returning to baseline by day 4 of the tolerance model. Mrgprd knockdown delayed the onset of tolerance, whereas AAV-mediated Mrgprd overexpression accelerated its development. Morphine treatment also decreased c-Jun expression by ∼40% at 24 h, consistent with the observed suppression of Mrgprd. In vivo siJun (siRNA targeting Jun mRNA to silence c-Jun expression) suppressed Mrgprd expression in DRG, and ChIP-qPCR and luciferase assays confirmed c-Jun binding to the Mrgprd promoter. Mrgprd knockdown increased Oprm1 mRNA and MOR protein concentrations. Approximately 50% increase in DS-lncRNA after Mrgprd suppression was observed in parallel with decreased Ehmt2/G9a expression, thereby relieving repression of Oprm1/MOR. DS-lncRNA knockdown restored Ehmt2 expression and reduced Oprm1 concentrations, reinstating tolerance in Mrgprd knockout mice. CONCLUSIONS: These findings reveal a peripheral pathway (c-Jun-Mrgprd-DS-lncRNA-Ehmt2/G9a-Oprm1/MOR) that modulates opioid responsiveness. Targeting this axis offers new potential therapeutic strategies to mitigate tolerance and improve the durability of opioid analgesia.

BACKGROUND: Accurate monitoring of the depth of anaesthesia is essential for patient safety. Although processed electroencephalogram monitoring is widely used, it is not always available. This study aimed to predict episodes of inadequate anaesthesia, defined as a bispectral index (BIS) value >60, by characterising heart rate (HR) dynamics. METHODS: Electrocardiogram data from 3338 surgical patients were analysed. BIS >60 events were identified, and the HR segments preceding these events at 0, 5, 10, and 15 min were extracted. Time-series features were extracted using a highly comparative time-series analysis framework. Gradient boosting models were trained and evaluated using a nested 10-fold cross-validation. A feature-reduction procedure was used to identify a compact feature subset. RESULTS: All models demonstrated strong discriminative performance, with area under the receiver operating characteristic curve values of 0.953 (95% confidence interval: 0.949-0.958) at 0 min, 0.917 (0.909-0.925) at 5 min, 0.910 (0.905-0.916) at 10 min, and 0.903 (0.894-0.912) at 15 min. A compact model comprising 27 features maintained high performance across all time points while achieving a 110-fold improvement in computational speed. These features predominantly captured fractal HR dynamics. CONCLUSIONS: High-dimensional descriptors of heart rate dynamics enabled accurate prediction of BIS >60 events. By identifying a compact subset of 27 features, this approach demonstrates potential as a clinically feasible and computationally efficient tool for monitoring the depth of anaesthesia.

BACKGROUND: Laboratory research suggests that vasopressin restores systemic arterial pressure without significantly increasing pulmonary artery pressures, compared with norepinephrine. We therefore tested the hypotheses that treatment of intraoperative vasoplegia with vasopressin rather than norepinephrine induces less pulmonary hypertension and improves right ventricular function during cardiac surgery. METHODS: Our single-center cluster-randomized multiple cross-over trial enrolled patients having elective cardiac surgery who developed systemic hypotension (mean arterial pressure <70 mmHg) and cardiac index greater than 2.2 L/min/m RESULTS: We analyzed 153 patients, with 70 assigned to vasopressin and 83 to norepinephrine. There were no significant differences in mPAP-to-MAP ratio [0.02 (95% CI: -0.02, 0.05; P = 0.646)] or in right ventricular free wall strain [3.45 (95% CI: 0.17, 6.73; P = 0.078) %] in patients given vasopressin vs norepinephrine infusion. There was no evidence of an interaction between preoperative pulmonary hypertension status and mPAP-to-MAP ratio (interaction P value = 0.781) or right ventricular strain (interaction P value = 0.780). CONCLUSION: We found no evidence to support the preferential use of Vasopressin over norepinephrine in cardiac surgery patients.