Anesthesia/surgery activate MMP9 leading to blood-brain barrier disruption, triggering neuroinflammation and POD-like behavior in aged mice.

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Analgesic Effects of Different Local Infiltration Anesthesia Techniques Combined with Femoral Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Clinical Trial.

Objective: Pain after total knee arthroplasty (TKA) remains an unresolved problem. Femoral nerve block (FNB) could relieve pain; however, it alone is insufficient. The local infiltration anesthesia technique (LIA) has been suggested as a supplement to FNB. This study aimed to evaluate the analgesic effects of different LIA combined with FNB in TKA patients. Methods: The femoral nerve was blocked with 0.375% ropivacaine 20mL, and all patients routinely received general anesthesia. The primary indicator was the proportion of patients who did not receive post-operative remedial analgesia. Seventy-eight patients were randomly assigned to PAI (periarticular injection combined with FNB), IAI (intra-articular injection combined with FNB), or control (FNB alone) groups. All patients underwent FNB under general anesthesia. The primary outcome was the proportion of patients who did not receive additional postoperative analgesia within the first 48 h after surgery. Results: Compared with the PAI and control groups, the IAI group had a higher proportion (69.23%) of patients who did not receive remedial analgesia within 48 hours after surgery (P = 0.009; P = 0.009), a lower consumption of diclofenac sodium lidocaine (P = 0.021; P < 0.001), and an earlier time of walking with a walker (P < 0.001; P < 0.001). The time of first need for remedial analgesia postoperatively in IAI group was longer than the PAI group (P = 0.008) and IAI group has a shorter hospital stay than the control group (P = 0.008). The maximum NRS during the first 48 hours postoperatively and NRS 24 hours after surgery in the IAI group were lower than those in the control and PAI groups. The incidences of POD and PONV were similar among the three groups (P = 0.610; P = 0.264). Conclusion: When combined with FNB, intra-articular injection offers a superior analgesic effect and favorable recovery compared to periarticular injection and separate application of FNB.

Active control of terahertz surface plasmonic wave excitation using electromagnetically induced transparency based graphene metasurfaces.

Surface plasmonic waves (SPWs) that propagate at meta-dielectric interface are a good source of information carrier waves for on-chip photonic devices, where SPW excitation is one key procedure. Recently, controlling SPW excitation using metasurface methods has drawn considerable attention owing to their design flexibility, wherein achieving dynamic control is of great importance. However, most studies in the terahertz regime so far are working in a passive way or only dynamically controllable at the propagation process. In this work, an active design for controlling terahertz SPWs at the excitation process is proposed using graphene metasurfaces based on the manipulation of the electromagnetically induced transparency (EIT) effect. Large modulation depth with controllable SPW excitations is demonstrated. Our method is flexible and promising in achieving more controlling degree of freedom, which can find broadband applications in future integrated devices and systems.

Exploiting the "Hot-Spots" of Hsp70-Bim Protein-Protein Interaction to Optimize the 1-Oxo-1H-phenalene-2,3-dicarbonitrile Analogues as Specific Hsp70-Bim Inhibitors.

Selectively targeting the cancer-specific protein-protein interaction (PPI) between Hsp70 and Bim has been discovered as a promising strategy for treating chronic myeloid leukemia (CML). The first Hsp70-Bim PPI inhibitor, S1g-2, has been identified to overcome the on-target toxicity of known Hsp70 inhibitors when it induces apoptosis of CML cells. Herein, we carried out a hit-to-lead optimization of S1g-2, yielding S1g-10, which exhibited a 10-fold increase in Hsp70/Bim suppressing potency. Furthermore, S1g-10 not only exhibited a 5- to 10-fold stronger antitumor activity in the sub-µM range against CML cells than S1g-2 in vitro, but it also overcame BCR-ABL-independent tyrosine kinase inhibitor resistance in CML in vivo depending on the Hsp70-Bim signaling pathway. Moreover, through structure-activity relationship analysis, TROSY-HSQC NMR, molecular dynamics simulation, and point mutation validation, two hydrophobic pockets composed of eight key residues were demonstrated to produce predominant interactions with either Bim or S1g-10, regarded as the "hot-spots" in the Hsp70-Bim PPI interface.

A Novel Opioid-Sparing Analgesia Following Thoracoscopic Surgery: A Non-Inferiority Trial.

Purpose: This randomized, non-inferiority study aimed to observe the feasibility of opioid-sparing analgesia based on modified intercostal nerve block (MINB) following thoracoscopic surgery. Patients and Methods: 60 patients scheduled for single-port thoracoscopic lobectomy were randomized to the intervention group or control group. After MINB was performed in both groups at the end of the surgery, the intervention group received patient controlled-intravenous analgesia (PCIA) of dexmedetomidine 0.05 µg/kg/h for 72 h after surgery, and the control group received conventional PCIA of sufentanil 3 µg/kg for 72 h. The primary outcome was a visual analog scale (VAS) on coughing 24 h after surgery. Secondary outcomes included the time to first analgesic request, pressing times of PCIA, time to first flatus, and hospital stay. Results: There was no difference in the cough-VAS at 24 h (median [interquartile range]) between the intervention group [3 (2-4)] and control group [3 (2-4), P = 0.36]. The median difference (95% CI) in the cough-VAS at 24 h was [0 (0 to 1), P = 0.36]. There was no significant difference in the time to first analgesic request, pressing times of PCIA, and hospital stay between groups (P > 0.05). A significant decrease in time to first flatus was observed in the intervention group (P < 0.01). Conclusion: Opioid-sparing analgesia provided safe and analogous postoperative analgesia with a shortened time to first flatus, compared with sufentanil-based analgesia in thoracoscopic surgery. This might be a novel method recommended for thoracoscopic surgery.

The Efficiency of Multipoint Rectus Sheath Block Based on Incision Location in Laparoscopic-Assisted Colorectal Surgery: A Randomized Clinical Trial.

BACKGROUND: Laparoscopic-assisted colorectal surgery is an effective surgery to treat colorectal cancer. During the laparoscopic-assisted colorectal surgery, a midline incision and several trocar insertions are required during the surgery. OBJECTIVE: To observe whether the rectus sheath block based on the locations of the surgical incision and trocars can significantly reduce the pain score on the first day after surgery. DESIGN: This study was a prospective, double-blinded, randomized controlled trial approved by the Ethics Committee of First Affiliated Hospital of Anhui Medical University (registration number: ChiCTR2100044684). SETTINGS: All patients were recruited from 1 hospital. PATIENTS: Forty-six patients aged 18 to 75 years undergoing elective laparoscopic-assisted colorectal surgery were successfully recruited, and 44 patients completed the trial. INTERVENTIONS: Patients in the experimental group received rectus sheath block, with 0.4% ropivacaine 40 to 50 mL, whereas the control group received an equal volume of normal saline. MAIN OUTCOME MEASURES: The primary outcome was pain score on postoperative day 1. Secondary outcomes included patient-controlled analgesia use at 24 and 48 hours after surgery and pain score at 6, 12, and 48 hours after surgery. RESULTS: Pain scores at rest and during activity at 6, 12, 24, and 48 hours after surgery and patient-controlled analgesia consumption of patients on the first day after surgery were significantly lower in the experimental group than those in the control group (all p < 0.05). LIMITATIONS: We did not separate pain into visceral and somatic pain because patients often had difficulty differentiating the source of pain. CONCLUSIONS: Our research indicates that in the context of multimodal analgesia, the rectus sheath block according to the midline incision and the positions of the trocars can reduce the pain scores and consumption of analgesic drugs on the first day after surgery for patients undergoing laparoscopic-assisted colorectal surgery. LA EFICIENCIA DEL BLOQUEO DE LA VAINA DEL RECTO DE VARIOS PUNTOS SEGN LA UBICACIN DE LA INCISIN EN LA CIRUGA COLORRECTAL ASISTIDA POR LAPAROSCOPIA UN ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La cirugía colorrectal asistida por laparoscopia es una cirugía eficaz para tratar el cáncer colorrectal. Durante la cirugía colorrectal asistida por laparoscopia, se requiere una incisión en la línea media y varias inserciones de trócaresOBJETIVO:El propósito de nuestro estudio fue observar si el bloqueo de la vaina del recto basado en las ubicaciones de la incisión quirúrgica y los trocares puede reducir significativamente la puntuación del dolor en el primer día después de la cirugía.DISEÑO:Este estudio fue un ensayo controlado aleatorio prospectivo, doble ciego, aprobado por el Comité de Ética del Primer Hospital Afiliado de la Universidad Médica de Anhui (número de registro: ChiCTR2100044684).ESCENARIO:Todos los pacientes fueron reclutados en un hospital.PACIENTES:Cuarenta y seis pacientes de 18 a 75 años de edad que se sometieron a cirugía colorrectal electiva asistida por laparoscopía fueron reclutados con éxito y cuarenta y cuatro pacientes completaron el ensayo.INTERVENCIONES:Los pacientes del grupo experimental recibieron bloqueo de la vaina del recto con 40-50 ml de ropivacaína al 0.4%, mientras que el grupo de control recibió el mismo volumen de solución salina normal.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la puntuación del dolor en el día 1 postoperatorio. Los resultados secundarios incluyeron el uso de analgesia controlada por el paciente a las 24 y 48 horas después de la cirugía y la puntuación del dolor a las 6, 12, y 48 horas después de la cirugía.RESULTADOS:Las puntuaciones de dolor en reposo y durante la actividad a las 6, 12, 24, y 48 horas después de la cirugía, y el consumo de PCA de los pacientes el primer día después de la cirugía fueron significativamente más bajos en el grupo experimental que en el grupo control (todos p < 0.05).LIMITACIONES:No separamos el dolor en dolor visceral y somático porque los pacientes a menudo tenían dificultades para diferenciar la fuente del dolor.CONCLUSIONES:Nuestra investigación indica que, en el contexto de la analgesia multimodal, el bloqueo de la vaina del recto de acuerdo con la incisión de la línea media y las posiciones de los trócares pueden reducir los puntajes de dolor y el consumo de analgésicos en el primer día después de la cirugía para pacientes sometidos a cirugía colorrectal laparoscópica. (Traducción-Dr. Jorge Silva Velazco ).

Opioid-Sparing Effect of Multi-Point Incision-Based Rectus Sheath Block in Laparoscopic-Assisted Radical Gastrectomy: A Randomized Clinical Trial.

BACKGROUND: Profound trauma from laparoscopic-assisted gastrectomy (LAG) requires medication with a large number of opioids. The purpose of our study was to observe whether an incision-based rectus sheath block (IBRSB) based on the locations of the surgical incision could significantly reduce the consumption of remifentanil during LAG. METHODS: A total of 76 patients were included. The patients were prospectively randomized into two groups. Patients in group IBRSB (n = 38) received ultrasound-guided IBRSB, and the patients received 0.4% ropivacaine 40-50 mL. Patients in group C (n = 38) received the same IBRSB with 40-50 mL normal saline. The following were recorded: the consumption of remifentanil and sufentanil during surgery, pain scores at rest and during conscious activity in the post-anesthesia care unit (PACU) and at 6, 12, 24, and 48 h after surgery, and use of the patient-controlled analgesia (PCA) at 24 and 48 h after surgery. RESULTS: A total of 60 participants completed the trial. The consumption of remifentanil and sufentanil in group IBRSB were significantly lower than that in group C (p < 0.001). Pain scores at rest and during conscious activity in the PACU and at 6, 12, 24, and 48 h after surgery and patients' PCA consumption within 48 h of surgery were significantly lower in group IBRSB than in group C (all p < 0.05). CONCLUSIONS: IBRSB based on incision multimodal anesthesia can effectively reduce the consumption of opioids during LAG, improving the postoperative analgesic effect and increasing patients' satisfaction.

Reactive oxygen species contribute to delirium-like behavior by activating CypA/MMP9 signaling and inducing blood-brain barrier impairment in aged mice following anesthesia and surgery.

Postoperative delirium (POD) is common in the elderly and is associated with poor clinical outcomes. Reactive oxygen species (ROS) and blood-brain barrier (BBB) damage have been implicated in the development of POD, but the association between these two factors and the potential mechanism is not clear. Cyclophilin A (CypA) is a specifically chemotactic leukocyte factor that can be secreted in response to ROS, which activates matrix metalloproteinase 9 (MMP9) and mediates BBB breakdown. We, therefore, hypothesized that ROS may contribute to anesthesia/surgery-induced BBB damage and delirium-like behavior via the CypA/MMP9 pathway. To test these hypotheses, 16-month-old mice were subjected to laparotomy under 3% sevoflurane anesthesia (anesthesia/surgery) for 3 h. ROS scavenger (N-acetyl-cysteine) and CypA inhibitor (Cyclosporin A) were used 0.5 h before anesthesia/surgery. A battery of behavior tests (buried food test, open field test, and Y maze test) was employed to evaluate behavioral changes at 24 h before and after surgery in the mice. Levels of tight junction proteins, CypA, MMP9, postsynaptic density protein (PSD)-95, and synaptophysin in the prefrontal cortex were assessed by western blotting. The amounts of ROS and IgG in the cortex of mice were observed by fluorescent staining. The concentration of S100ß in the serum was detected by ELISA. ROS scavenger prevented the reduction in TJ proteins and restored the permeability of BBB as well as reduced the levels of CypA/MMP9, and further alleviated delirium-like behavior induced by anesthesia/surgery. Furthermore, the CypA inhibitor abolished the increased levels of CypA/MMP, which reversed BBB damage and ameliorated delirium-like behavior caused by ROS accumulation. Our findings demonstrated that ROS may participate in regulating BBB permeability in aged mice with POD via the CypA/MMP9 pathway, suggesting that CypA may be a potential molecular target for preventing POD.

Atomic-level flatness on oxygen-free copper surface in lapping and chemical mechanical polishing.

Oxygen-free copper (OFC) serves as a core component of high-end manufacturing, and requires high surface quality. It is always a significant challenge to manufacture high-quality atomic-level surfaces. In this study, SiO2 nanospheres with good dispersibility were prepared and a late-model environmentally friendly chemical mechanical polishing (CMP) slurry was developed. The CMP slurry consists of SiO2 nanospheres, CeO2 nanospheres, H2O2, NaHCO3, polyaspartic acid and deionized water. After CMP, the average roughness (Sa) of the OFC wafer reached 0.092 nm with an area of 50 × 50 µm2. Atomic-level flatness on the oxygen-free copper surface was acquired, which has never been reported before. Moreover, the mechanical removal mechanism of abrasive particles and the chemical reactions during lapping and CMP are proposed in detail. The thickness and composition of the damaged layer after lapping and polishing were analyzed. The lapping-damaged layer consists of a lattice distortion region, moiré fringes, grain boundary, superlattice and edge dislocations, and the polishing-damaged layer contains a handful of stacking faults with single-layer or multi-layer atoms. The chemical action involves three reactions: oxidation, corrosion and chelation. The processing method and its mechanistic explanation pave the way for the fabrication of high-performance OFC surfaces for use in vacuum, aerospace, military and electronic industries.

Propofol Versus Sevoflurane General Anaesthesia for Selective Impairment of Attention Networks After Gynaecological Surgery in Middle-Aged Women: A Randomised Controlled Trial.

Purpose: Attention is an essential component of cognitive function that may be impaired after surgery with anaesthesia. Propofol intravenous anaesthesia and sevoflurane inhalational anaesthesia are frequently used in gynaecological surgery. However, which type of anaesthetic has fewer cognitive effects postoperatively remains unclear. We compared the differences in attention network impairment after surgery in women receiving propofol versus sevoflurane general anaesthesia. Patients and Methods: Eighty-three patients with gynaecological diseases who were 40-60 years of age were involved in the study. All patients underwent elective gynaecological surgery under either total intravenous anaesthesia or sevoflurane inhalational anaesthesia, depending on randomisation. The efficiencies of the three attention networks were captured using the attention network test preoperatively and on the 1st and 5th postoperative days. Results: Both groups of patients showed differences in impairments on the 1st and 5th postoperative days. Pairwise comparisons indicated that the alerting and orienting networks of patients in the propofol group were impaired to a greater extent than those of patients in the sevoflurane group on the 1st postoperative day, while the executive control network was impaired to a lesser extent. On the 5th postoperative day, the alerting networks of both groups recovered to the baseline level. Patients in the propofol group still showed impairment of the orienting network, while patients in the sevoflurane group recovered to baseline. For the executive control network, patients in the sevoflurane group still exhibited more severe impairment than those in the propofol group. Conclusion: In middle-aged women, propofol impaired orienting and alerting networks more than sevoflurane, while sevoflurane showed more residual impairment of the executive control network.

Caloric Restriction Alleviates CFA-Induced Inflammatory Pain via Elevating ß-Hydroxybutyric Acid Expression and Restoring Autophagic Flux in the Spinal Cord.

Inflammatory pain is the most common type of pain encountered in clinical practice; however, the currently available treatments are limited by insufficient efficacy and side effects. Therefore, new methods to relieve inflammatory pain targeting new mechanisms are urgently needed. Preclinical investigations have shown that CR (calorie restriction) exerts analgesic effects in neuropathic and cancer pain; however, the effect of CR on chronic inflammatory pain remains unknown. During calorie restriction, autophagy, a lysosome-dependent degradation process, can be activated to support cell survival. In the present study, we investigated the analgesic effects of CR on complete Freund's adjuvant (CFA)-induced inflammatory pain. The accumulation of LC3-II and p62 showed impaired autophagic flux in the ipsilateral spinal cord of mice with CFA-induced inflammatory pain. CR alleviated mechanical allodynia and thermal hyperalgesia and reduced paw edema and pro-inflammatory factors following CFA administration. CR exerted an analgesic effect by restoring autophagic flux in the spinal cord. Regarding the mechanisms underlying the analgesic effects of CR, ß-hydroxybutyric acid (BHB) was studied. CR increased BHB levels in the ipsilateral spinal cord. Furthermore, exogenous BHB administration exerted an analgesic effect by restoring autophagic flux in the spinal cords of CFA-induced inflammatory pain mice. Taken together, these results illustrated that CR relieved inflammatory pain by restoring autophagic flux in the spinal cord, while BHB controlled the benefits of CR, suggesting that CR or BHB might be a promising treatment for inflammatory pain.

Dexmedetomidine Combined with Femoral Nerve Block Provides Effective Analgesia Similar to Femoral Nerve Combined with Sciatic Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Study.

BACKGROUND: Total knee arthroplasty (TKA) is a severe traumatic procedure, and femoral nerve block (FNB) combined with a sciatic nerve block (SNB) is widely used in TKA. However, injury of the sciatic nerve is clinically reported. Dexmedetomidine (DEX) could reduce stress and inflammation, as well as improve pain in TKA. This study aims to observe the analgesic impact of DEX combined with FNB in TKA. METHODS: Eighty-eight patients undergoing TKA were included and randomly divided into two groups: DF group (FNB combined with DEX 0.6µg/kg before surgery, followed by DEX 0.2-0.4µg/kg/h until articular closure) and SF group (FNB combined with SNB). Each nerve was blocked with 0.375% ropivacaine 20mL, and all patients received general anesthesia routinely. The primary endpoint was the pain visual analog scale (VAS) score during activities at postoperative 24 hours. RESULTS: There was no statistical difference in the pain VAS scores at any time point. The mean duration of analgesia for patients with rescue analgesic requests was comparable between the two groups: 25.4 ± 6.3 hours in the DF group vs 24.8 ± 6.4 hours in the SF group (two-sample t-test, p=0.738). The total dose of sufentanil was similar between groups (P=0.355). The maintenance dose of propofol and dose of rescue analgesics were comparable (all P>0.05). There were no statistical differences in the incidence of adverse events. However, the time to extubate in the DF group was significantly longer than those in the SF group (P<0.001). CONCLUSION: DEX combined with FNB could provide effective analgesia similar to SNB combined with FNB in TKA. CLINICAL TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on November 17, 2019 (identifier: ChiCTR1900027552).

God is in the rain: The impact of rainfall-induced early social distancing on COVID-19 outbreaks.

We measure the benefit to society created by preventing COVID-19 deaths through a marginal increase in early social distancing. We exploit county-level rainfall on the last weekend before statewide lockdown in the early phase of the pandemic. After controlling for historical rainfall, temperature, and state fixed-effects, current rainfall is a plausibly exogenous instrument for social distancing. A one percent decrease in the population leaving home on the weekend before lockdown creates an average of 132 dollars of benefit per county resident within 2 weeks. The impacts of earlier distancing compound over time and mainly arise from lowering the risk of a major outbreak, yielding large but unevenly distributed social benefit.

Effect of Different Modes of Administration of Dexmedetomidine Combined with Nerve Block on Postoperative Analgesia in Total Knee Arthroplasty.

INTRODUCTION: Dexmedetomidine (DEX) as a nerve block adjuvant can significantly prolong analgesia. However, whether perineural or systemic administration of DEX is more beneficial in patients undergoing total knee arthroplasty (TKA) has not been thoroughly investigated. To this end, we evaluated the effects of perineural and systemic DEX administration on postoperative analgesia in patients undergoing TKA surgery. METHODS: We randomly assigned patients undergoing TKA under general anesthesia combined with femoral nerve block and sciatic nerve block to one of three groups: (1) ropivacaine plus perineural dexmedetomidine (DP): 0.25% ropivacaine 40 mL plus 0.5 µg/kg dexmedetomidine; (2) ropivacaine plus systemic dexmedetomidine (DS): 0.25% ropivacaine 40 mL plus systemic 0.5 µg/kg dexmedetomidine; (3) control group (C): 0.25% ropivacaine 40 mL. RESULTS: The average length of time until patients first experienced postoperative pain was significantly longer in the DP group (26.0 h [22.0-30.0 h]) than in the DS group (22.4 h [18-26.8 h]) and the control group (22.9 h [19.5-26.3 h], P = 0.001). For this result there was no significant difference between the DS and the control group. Compared with the DS and control groups, patients in the DP group had lower resting visual analogue scale (VAS) scores at 24, 48, and 72 h after surgery (P < 0.05). VAS activity scores at 12, 24, and 48 h after surgery in the DP group were lower than those in the DS and control groups, with a statistically significant difference (P < 0.05). Compared with the DS and control groups, the amount of postoperative opioids in the DP group was also significantly reduced, and the number of people needing postoperative rescue analgesia was significantly lower, with a statistical difference (P < 0.05). Meanwhile, the sleep satisfaction of patients in the DP group on the first night after surgery and the satisfaction with pain control at 72 h after surgery were both higher than those in the DS group and control group (P < 0.05). CONCLUSIONS: Perineural administration of DEX can significantly prolong the interval until patients report pain for the first time after TKA, relieve postoperative pain, reduce postoperative opioid dosage, and improve postoperative sleep quality and satisfaction with pain control. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry, identifier ChiCTR1900025808.

Anti-nociceptive Effects of Dexmedetomidine Infusion Plus Modified Intercostal Nerve Block During Single-port Thoracoscopic Lobectomy: A Double-blind, Randomized Controlled Trial.

BACKGROUND: Multimodal general anesthesia based on modified intercostal nerve block (MINB) has been found as a novel method to achieve an intraoperative opioid-sparing effect. However, there is little information about the effective method to inhibit visceral nociceptive stress during single-port thoracoscopic surgery. OBJECTIVE: To investigate whether a low-dose dexmedetomidine infusion followed by MINB might be an alternative method to blunt visceral stress effectively. STUDY DESIGN: Double-blind, randomized control trial. SETTING: Affiliated hospital from March 2020 through September 2020. METHODS: Fifty-four patients were randomized (1:1), 45 patients were included to receive dexmedetomidine with a 0.4 microgram/kg bolus followed by 0.4 microgram/kg/h infusion (group Dex) or saline placebo (group Con). During the operation, an additional dose of remifentanil 0.05-0.25 microgram/kg/min was used to keep mean arterial pressure (MAP) or heart rate (HR) values around 20% below baseline values. The primary outcome was to evaluate remifentanil consumption. Secondary outcomes included intraoperative hemodynamics, the first time to press an analgesia pump, and adverse effects. RESULTS: Remifentanil consumption during surgery was markedly decreased in the Dex group than in the Con group (0 [0-0] versus 560.0 [337.5-965.0] microgram; P = 0.00). MAP and HR in the Con group during the first 5 minutes after visceral exploration was significantly higher than in the Dex group (P < 0.05). Time to first opioid demand was significantly prolonged (P = 0.04) and postoperative length of stay was shortened slightly in the Dex group (P = 0.05). LIMITATIONS: This study was limited by the measurement of nociception. CONCLUSIONS: This study demonstrates that low-dose dexmedetomidine infusion combined with MINB might be an effective alternative method to blunt visceral stress in patients undergoing single-port thoracoscopic lobectomy. Furthermore, the analgesic effect of MINB was significantly prolonged after dexmedetomidine infusion.

Comparison of Effects between Combined Lumbar-Sacral Plexus Block plus General Anesthesia and Unilateral Spinal Anesthesia in Elderly Patients Undergoing Hip Fracture Surgery: A Pilot Randomized Controlled Trial.

PURPOSE: Hip fracture is a common injury in geriatric populations, which is associated with poor quality of life. However, the ideal anesthesia technique for this disease is yet to be identified. This study aimed to compare the combined lumbar-sacral plexus block (CLSB) plus general anesthesia (bispectral index (BIS) 60-80) with the unilateral spinal anesthesia (SA) on activity of daily living in elderly patients undergoing hip fracture surgery. METHODS: A total of 124 elderly patients undergoing hip fracture surgery were randomly assigned to two groups. Patients in the SA group received light-specific gravity spinal anesthesia, and patients in the CLSB group received lumbar and sacral plexus block with general anesthesia (BIS 60-80). The primary outcomes were 30-day activity of daily living (ADL). The secondary outcomes were postoperative pain scores, postoperative delirium, in-hospital cost, and major complications. RESULTS: The ADL scores of postoperative day 30 (POD30) in the CLSB group are higher than those in the SA group (27.34 ± 7.01 versus 24.70 ± 6.40, P=0.045). Compared to preoperative ADL scores, there were higher increased scores in the CLSB group than in POD30 (CLSB group 8.09 ± 3.39 versus SA group 4.87 ± 3.90, P < 0.001). Mild-to-moderate pain did not have differences between the two groups (rest pain: 3 versus 2, P=0.344; motion pain: 5 versus 4, P=0.073). There were no significant differences in incidence of postoperative delirium, PONV, and other complications. CONCLUSION: The unilateral SA can reduce the deterioration of ADL after hip fracture surgery and provide a better postoperative recovery.

Effects of Different Local Analgesic Techniques on Postoperative Quality of Life and Pain in Patients Undergoing Total Hip Arthroplasty Under General Anesthesia: A Randomized Controlled Trial.

BACKGROUND: Both lumbosacral plexus block (LSPB) and local infiltration analgesia (LIA) can provide postoperative analgesia for patients undergoing total hip arthroplasty (THA). The current study aimed to compare the differences between LSPB and LIA on postoperative pain and quality of life (QoL) in THA patients. METHODS: A total of 117 patients aged 40-80 years, ASA I-III, were prospectively randomized into two groups: a general anesthesia plus LSPB (Group LSPB) and a general anesthesia plus LIA (Group LIA). Pain intensity and opioid consumption were recorded Within 72 hours after surgery. QoL was measured by EQ-5D and EQ-VAS questionnaires, and the incidence of postoperative pain was measured as part of the EQ-5D on day 1, day 3, day 7, and month 1, month 3, and month 6 after surgery. RESULTS: EQ-5D scores: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression were higher in Group LSPB versus Group LIA throughout six-month follow-ups (p = 0.039). The pain intensity was lower in Group LSPB than in Group LIA 0-12 h after surgery (2.41 vs 2.79, p = 0.01), but was higher in Group LSPB than in Group LIA 12-24 h (2.59 vs 2.05, p = 0.02) and 24-48 h (2.18 vs 1.73, p = 0.02) after surgery. There were no differences in opioid consumption between the groups during the first 72 postoperative hours. In the first month after surgery, more patients in Group LSPB than in Group LIA had no pain (52 vs 40, p = 0.04). CONCLUSION: Both LSPB and LIA can provide satisfactory postoperative analgesia. The LSPB is better than LIA for long-term QoL in THA patients undergoing general anesthesia. CLINICAL TRIAL REGISTRATION NUMBER: The Chinese Clinical Trial Registry (ChiCTR-INR-17012545).

Comparison of Sevoflurane and Propofol on the Incidence of Postoperative Pain and Quality of Life in Patients Undergoing Total Knee Arthroplasty With Chronic Pain Before Surgery.

BACKGROUND: Propofol and sevoflurane as frequently used general anesthetics can affect postoperative pain. Our study explored whether the incidence of postoperative pain differed among patients with chronic pain undergoing total knee arthroplasty (TKA) anesthetized with sevoflurane or propofol. METHODS: Patients were randomly assigned to groups receiving either sevoflurane (Group S, n = 50) or propofol (Group P, n = 47) for anesthesia maintenance during TKA. The incidences of postoperative pain and quality of life (QoL) were measured using the EuroQol 5-Dimension (EQ-5D) scale at 1, 3, and 7 days post-operation (DPO), and 1 and 3 months post-operation (MPO). RESULTS: At 3 DPO, fewer patients reported moderate pain (P = 0.001) and more patients reported no pain (P = 0.003) in Group S than that in Group P. At 3 MPO, more patients reported no pain (P = 0.04) and fewer patients reported moderate pain (P = 0.04) in Group S than in Group P. No significant differences were found in the incidence of postoperative pain between the 2 groups of patients at the other time points. The EQ-5D scores were higher in Group S than in Group P (P = 0.022), and the difference was 0.15 at most, which was not optimal. The EQ-5D clinical results might be not very significant. CONCLUSIONS: Sevoflurane anesthesia may have potential advantages in reducing postoperative pain in patients undergoing TKA with a preoperative VAS score > 4.