Daily Anesthesiology Research Analysis

Sepsis is an immune dysregulation syndrome triggered by infection, characterized by host self-damage due to immune imbalances. This study focuses on dynamic changes of mitochondrial symbiotic function in host cells during sepsis and systematically investigates dysregulation of mitochondrial communication modes and the intrinsic link between mitochondrial DNA (mtDNA) release and immune dysregulation. We demonstrate that during early-stage LPS treatment, mitochondria actively remodel by extruding flagella-like extensions (termed mitoFLARE). These structures, nanotubes mediating long-distance transport, form through glycosylated TRAK1 binding FHL2 to drive actin network formation, thereby shifting mitochondrial communication from direct fusion to nanotube-mediated transport. This helps maintain dynamic exchange within the inner mitochondrial membrane under LPS treatment. However, as inflammation progresses, deteriorated mitochondrial quality control disrupts the MICOS-SAM complex, abrogates inner-outer membrane anchoring, and suppresses mitoFLARE functions. All these ultimately enhance endoplasmic reticulum-mitochondrial contacts to promote outer membrane rupture and result in mtDNA release into the cytoplasm to activate cGAS-STING signaling, further triggering immune dysregulation and inflammatory storm, culminating in programmed cell death and organ dysfunction. This study elucidates the pivotal role of dysregulated mitochondrial-host symbiosis in sepsis progression and provides important insights into the underlying mechanisms of sepsis-associated immune imbalances, laying a theoretical foundation for targeted therapy development.

INTRODUCTION: Rebound pain after peripheral nerve block is recognised increasingly as a postoperative complication that may diminish the benefits of regional anaesthesia. We undertook a systematic review and network meta-analysis to evaluate pharmacological strategies for its prevention. METHODS: We searched relevant databases for randomised controlled trials in adults undergoing surgery with peripheral nerve blocks. The primary outcome was the incidence of rebound pain. Secondary outcomes were: timing and severity of rebound pain; time to first rescue analgesia; patient satisfaction; sleep disturbance; and intervention-related adverse effects. RESULTS: Twenty-four randomised controlled trials (2130 patients, eight interventions) were included. Intravenous dexamethasone had the highest probability of reducing rebound pain incidence (surface under the cumulative ranking curve 0.91) and was judged 'definitely superior' to control. Perineural dexamethasone and perineural dexmedetomidine ranked highest for delaying rebound pain and prolonging time to first rescue analgesia. Pre-emptive opioids were probably inferior to control. Certainty of evidence ranged from very low to moderate. Data for pain severity, patient satisfaction and sleep disturbance were reported inconsistently and could not be pooled. DISCUSSION: Intravenous dexamethasone was the most effective intervention for preventing rebound pain following single-injection peripheral nerve blocks. Perineural dexamethasone and dexmedetomidine showed benefit in delaying onset and prolonging analgesia. These findings support intravenous dexamethasone as a first-line prophylactic drug, while highlighting the need for adequately powered trials of alternative strategies.

BACKGROUND: Total knee arthroplasty (TKA) is associated with significant postoperative pain. This study aimed to evaluate whether the combined intrathecal administration of morphine and fentanyl improves postoperative analgesia compared with either agent alone. METHODS: In this randomised controlled trial, 111 patients undergoing TKA under spinal anaesthesia were assigned to receive intrathecal fentanyl 25 µg (F group), morphine 100 µg (M group), or a combination of fentanyl 25 µg and morphine 100 µg (MF group). All groups received 12.5 mg of 0.5% hyperbaric bupivacaine. The primary outcome was the resting pain score at 6 h postoperatively. Secondary outcomes included pain scores (at rest and during movement) at 12 and 24 h, cumulative 24-h opioid consumption, opioid-related adverse effects, and intraoperative haemodynamic variables. RESULTS: At 6 h, resting pain scores were significantly lower in the MF group than in the F and M groups (1.5 ± 0.9 vs. 4.2 ± 2.7 and 2.7 ± 2.0; P < 0.001). Pain scores at rest and during motion at 6, 12, and 24 h were consistently lower in the MF group (P < 0.001). Cumulative 24-h morphine consumption was reduced in the MF group (10 ± 7 mg) compared with the F (30 ± 16 mg) and M (15 ± 9 mg) groups (P < 0.001). Nausea and vomiting were more frequent in the M and MF groups than in the F group, with no significant difference between the M and MF group. CONCLUSIONS: Combined intrathecal administration of morphine and fentanyl provided superior postoperative analgesia and reduced opioid consumption compared with either agent alone, without increasing opioid-related adverse effects compared with morphine alone. This strategy represents a viable analgesic option, particularly when peripheral nerve blocks are not feasible. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03365115; Date of registration: 30/11/2017).