Anesthesia and analgesia最新文献

Background: Many patients undergoing surgery experience accompanying pain symptoms preoperatively. The impact of painful stimuli on general anesthesia remains largely unknown. Corticotrophin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVN CRH neurons) are crucial central stress hubs that respond to painful stimuli. These neurons also participate in regulating processes such as sleep and anesthesia. Natural reward can inhibit PVN CRH neurons to relieve stress-induced behavioral changes, but the effect of natural reward on the anesthesia process in patients with pain is not clear. In this study, we assessed the impact of painful stimuli on isoflurane anesthesia and its potential neural mechanism. We also investigated the potential of natural reward therapy for alleviating the impact of painful stimuli on isoflurane anesthesia.

Methods: The righting reflex test and cortical electroencephalography (EEG) were used as measures of consciousness in complete Freund's adjuvant (CFA)-injected mice during isoflurane anesthesia. EEG and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. The expression of c-Fos, fiber photometry recording, and brain slice electrophysiology were used to determine neuronal activity changes in PVN CRH neurons after CFA injection or 10% sucrose treatment. Finally, chemogenetic technology was used to specifically manipulate PVN CRH neurons.

Results: Compared to the saline-injected mice, the CFA-injected mice exhibited an increased the mean[SD] induction time of isoflurane anesthesia (354[48] s vs 258[30] s, P = .0001) and a reduced BSR of isoflurane anesthesia (60.1[10.3] % vs 81.5[9.76] %, P = .002). CFA injection increased PVN c-Fos expression (3667[706] vs 1735[407], P = .0002) and enhanced the population activity of PVN CRH neurons (33.4[13.6] % vs 1.23[3.57] %, P = .0009). Chemogenetic suppression of PVN CRH neurons reversed the anesthesia abnormalities in CFA-injected mice. Natural reward accelerated the induction time of isoflurane anesthesia (252[24] s vs 324[36] s, P = .003) and increased the BSR of isoflurane anesthesia (84.8[5.36] % vs 57.7[14.3] %, P = .0005). Chemogenetic activation of PVN CRH neurons reversed the effect of natural reward on isoflurane anesthesia in CFA-injected mice.

Conclusions: Painful stimuli affect the process of isoflurane anesthesia by activating PVN CRH neurons, which implies that these neurons modulate isoflurane anesthesia. Additionally, natural reward alleviates the impact of painful stimuli on isoflurane anesthesia by inhibiting PVN CRH neurons.

Background: Total knee arthroplasty is frequently associated with postoperative pain. Continuous adductor canal blocks are widely used for postoperative analgesia. However, the high dislocation rate of nerve block catheters often leads to ineffective pain control. This study aimed to compare the analgesic effectiveness of repeated daily injections of adductor canal block up to postoperative day (POD) 2 and continuous adductor canal block in patients who underwent total knee arthroplasty.

Methods: Seventy-six patients who underwent total knee arthroplasty under spinal anesthesia were randomized to receive repeated daily adductor canal blocks at the end of surgery and in the morning of POD1 and POD2 (n = 39) or continuous adductor canal block with a patient-controlled bolus (n = 37). All patients received perioperative multimodal analgesia. The primary outcome was the time-weighted average numeric rating scale pain score at rest, measured from the end of surgery to 14:00 on POD2. Pain scores over time were also compared using generalized estimating equations.

Results: There was no significant difference in the time-weighted average pain score at rest (from POD0 to POD2) between the repeated injection group (2.9 ± 1.9) and the continuous group (3.1 ± 2.1; mean difference 0.09, 95% confidence interval [CI], -0.81 to 0.99; P = .842). Repeated daily injections did not reduce pain at rest or pain during movement after adjusting for time. In the continuous group, the cumulative occurrence of nerve block catheter dislocation was 48.6% (18/37) on POD1 and 62.2% (23/37) on POD2, as assessed using ultrasonography.

Conclusions: This study was unable to determine whether repeated daily injections or continuous adductor canal block provided superior analgesia in terms of the average pain score during the first 2 days after total knee arthroplasty. However, considering the high dislocation rate of nerve block catheters, reducing catheter dislodgement may improve the analgesic effectiveness of continuous adductor canal blocks.

Background: Volatile anesthetics are gaining attention as sedatives in intensive care units. Sedation is a significant risk factor for skeletal muscle atrophy and weakness in critically ill patients; however, volatile anesthetics' influence on skeletal muscle atrophy remains unclear. Therefore, we investigated their effects on skeletal muscle mass using a murine-derived muscle cell line and mice.

Methods: C2C12 myotubes were exposed to isoflurane or sevoflurane. Myotube diameter was assessed using immunofluorescence. The expression levels of Atrogin-1, MuRF1, and LC3-II and phosphorylation levels of p70 S6K and Akt were analyzed to evaluate protein degradation and synthesis. To determine whether these effects were mediated through the Akt pathway, experiments with insulin-like growth factor 1 (IGF-1) were performed. Furthermore, mice skeletal muscle exposed to isoflurane or sevoflurane were compared with control mice and short-term immobility mice induced by sciatic nerve denervation (DN) or hindlimb suspension (HS).

Results: Exposure of C2C12 myotubes to 2.8% isoflurane or 5.0% sevoflurane reduced the myotube diameter by 14.4 µm (95% confidential interval [CI], 11.7-17.1, P < .001) and 13.2 µm (95% CI, 10.1-16.2, P < .001), respectively. Exposure to 2.8% isoflurane increased the expressions of Atrogin-1 (2.9-fold [95% CI, 2.1- to 3.8-fold], P < .001), MuRF1 (3.1-fold [95% CI, 2.4- to 3.8-fold], P < .001), and LC3-II (1.6-fold [95% CI, 1.4- to 1.8-fold], P < .001), whereas decreasing phosphorylation of p70 S6K (0.3-fold [95% CI, 0.2- to 0.4-fold], P < .001) and Akt (0.4-fold [95% CI, 0.3- to 0.5-fold], P < .001). Exposure to 5.0% sevoflurane resulted in similar effects. Additionally, IGF-1 counteracted the effects of isoflurane on myotube mass. In mice skeletal muscle, exposure to 1% isoflurane or 1.5% sevoflurane decreased Akt phosphorylation (isoflurane: 0.4-fold [95% CI, 0.1- to 0.8-fold], P = .003; sevoflurane: 0.5-fold [95% CI, 0.4- to 0.6-fold], P = .011) and increased the expression levels of Atrogin-1 (isoflurane: 4.1-fold [95% CI, 3.2- to 5.1-fold], P < .001; sevoflurane: 2.3-fold [95% CI, 1.1- to 3.5-fold], P = .026), MuRF1 (isoflurane: 2.7-fold [95% CI, 1.3- to 4.1-fold], P = .01; sevoflurane: 2.3-fold [95% CI, 1.0- to 3.7-fold], P = .022), and LC3-II (isoflurane: 1.9-fold [95% CI, 0.9- to 3.0-fold], P = .045; sevoflurane: 1.5-fold [95% CI, 1.4- to 1.6-fold], P < .001) while decreasing p70 S6K phosphorylation (isoflurane: 0.5-fold [95% CI, 0.4- to 0.6-fold], P = .013; sevoflurane: 0.7-fold [95% CI, 0.6- to 0.8-fold], P = .008) compared with DN. Similar results were observed when comparing between isoflurane or sevoflurane exposure and HS.

Conclusions: Volatile anesthetics induce skeletal muscle atrophy by downregulating the Akt pathway, suggesting they may exacerbate skeletal muscle atrophy beyond immobility effects.