The impact of IPACK combined with adductor canal block under ultrasound guidance on early motor function after total knee arthroplasty.

BACKGROUND: This study aimed to evaluate the impact of Infiltration between the Popliteal Artery and Capsule of the posterior Knee (IPACK) combined with an adductor canal block under the guidance of ultrasound on early motor function after Total Knee Arthroplasty (TKA). METHODS: A sample of 60 cases who were scheduled for elective unilateral TKA were divided into two groups using random number table method: a group with IPACK combined with an adductor canal block (I group, n = 30), and a group with femoral nerve block combined with superior popliteal sciatic nerve block (FS group, n = 30). Before anesthesia induction was completed, the patients in I group received an ultrasound-guided adductor canal block with 15 mL of 0.375% ropivacaine and an IPACK block with 25 mL of ropivacaine, and the patients in FS group received a femoral nerve block and a superior popliteal sciatic nerve block with 20 mL of 0.375% ropivacaine under ultrasound guidance. Post-operation, all the patients received patient-controlled intravenous analgesia combined with an oral celecoxib capsule to relieve pain and maintain a visual analogue scale score of ≤ 3. RESULTS: The quadriceps femoris muscle strength score was significantly higher in Ⅰ group than in FS group (p = 0.001), while the modified Bromage score were significantly lower and walking distance results were significantly higher in Ⅰ group than in FS group (both p = 0.000). CONCLUSION: Compared with femoral nerve block combined with superior popliteal sciatic nerve block, IPACK combined with adductor canal block had a mild impact on early motor functions after TKA.

Perioperative intravenous S(+)-ketamine for acute postoperative pain in adults: study protocol for a multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A trial).

INTRODUCTION: Postoperative pain remains incompletely controlled for decades. Recently, multimodal analgesia is emerging as a potential approach in the management of postoperative pain. Therein, S(+)-ketamine is appealing as an adjuvant drug in multimodal analgesia due to its unique pharmacological advantages. This pragmatic clinical trial (SAFE-SK-A trial) is designed to investigate the analgesic effect and safety of S(+)-ketamine for acute postoperative pain in adults and explore the optimal strategy of perioperative intravenous S(+)-ketamine in a real-world setting. METHODS AND ANALYSIS: This multicentre, randomised, open-label, positive-controlled, pragmatic clinical trial (SAFE-SK-A study) is planned to conduct in 80 centres from China and recruit a total of 12 000 adult participants undergoing a surgical procedure under general anaesthesia. Patient recruitment started in June 2021 and will end in June 2022. Participants will be randomised in a ratio of 2:1 to either receive perioperative intravenous S(+)-ketamine plus conventional anaesthesia or conventional anaesthesia only. Given the pragmatic nature of the study, no specific restriction as to the administration dosage, route, time, synergistic regimen or basic analgesics. Primary endpoints are the area under the broken line of Numerical Rating Scale (NRS) scores for pain intensity and the total opioid consumption within 48 hours postoperative. Secondary endpoints are postoperative NRS scores, the anaesthesia recovery time, time of first rescue analgesia, the incidence of rescue analgesia, the incidence of postoperative delirium, patient questionnaire for effect, changes from baseline in cognitive function and anxiety and depression, as well as the adverse events and pharmacoeconomic outcomes. The general linear model will be used for the primary endpoint, and appropriate methods will be used for the secondary endpoints. ETHICS AND DISSEMINATION: This trial has been approved by the local Institutional Review Board (S2021-026-02) and conducted following the Declaration of Helsinki. Results of this trial will be publicly disclosed and published in scientific journals. TRIAL REGISTRATION NUMBER: NCT04837170; Pre-results.

Hemoglobin Concentration and Post-Operative Delirium in Elderly Patients Undergoing Femoral Neck Fracture Surgery.

This study aimed to determine the relationship between hemoglobin (Hb) concentration and post-operative delirium (POD) in elderly patients undergoing femoral neck fracture (FNF) surgery and to investigate whether the change in Hb concentration is associated with POD and the risk factors for POD. A total of 889 patients admitted with FNF between January 2016 and December 2020 were enrolled in this single-center, retrospective, case-control study. Hb concentrations were determined at admission and post-operative day 1 and the change in Hb concentration was defined as the absolute value of difference in pre-operative and post-operative Hb concentration. POD was assessed using the Confusion Assessment Method for the Intensive Care Unit (ICU) or the Confusion Assessment Method once a daily after surgery. The logistic regression analysis was performed for statistical analysis. In total, 172 (19.3%) patients developed POD and 151 (87.8%) patients developed POD within post-operative 3 days. Low pre-operative Hb concentration [p = 0.026, odds ratio (OR) = 0.978] and significant change in Hb concentration (p = 0.006, OR = 1.033) were significantly associated with POD. After excluding change in Hb concentration or pre-operative Hb concentration, neither of them was significantly associated with POD (p > 0.05). The interaction analysis of change in Hb concentration and pre-operative Hb concentration in the logistic regression model was negative. There was no significant relationship between post-operative Hb concentration and POD. Age (p < 0.001, OR = 1.072), stroke history (p = 0.003, OR = 2.489), post-operative ICU transfer (p = 0.007, OR = 1.981), and visual analog scale score within post-operative 2 days (p 1 = 0.016 and p 2 = 0.006) were independently associated with POD in the logistic regression analysis. Patients with low pre-operative Hb concentrations and high changes in Hb concentration seem to have an increased risk of POD and should receive more attention. Old age, stroke history, post-operative ICU transfer, and pain within post-operative 2 days were significantly associated with POD.

Effect of NMDAR-NMNAT1/2 pathway on neuronal cell damage and cognitive impairment of sevoflurane-induced aged rats.

Objective: The possible effect of NMDAR (N-methyl-D-aspartate receptor)-NMNAT1/2 (nicotinamide/nicotinic acid mono-nucleotide adenylyltransferase) signaling pathway on the neuronal cell damage and cognitive impairment of aged rats anesthetized by sevoflurane was explored.Methods: Adult male Wistar rats were selected and divided into Control, Sevo (Sevoflurane), Sevo+DCS (NMDAR agonist D-cycloserine) 30 mg/kg, Sevo+DCS 100 mg/kg, and Sevo+DCS 200 mg/kg groups. Morris water maze and fear conditioning text were used to observe cognitive function changes of rats. The inflammatory cytokines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) assay, neuronal apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining and MDAR-NMNAT1/2 pathway-related proteins by Western blotting.Results: The longer escape latency, decreased platform crossing times and reduced staying time spent in platform quadrant were found in rats from Sevo group, with decreased percentage of freezing time in contextual test and tone cued test; and meanwhile, these rats had increased inflammatory cytokines (interleukin (IL)-1ß, tumor necrosis factor (TNF-α), IL-6, and IL-8) and neuronal apoptosis, but declined expressions of MDAR-NMNAT1/2 pathway-related proteins. However, the above changes were exhibited an opposite tendency in those Sevo rats treated with different concentrations of DCS (including 30, 100, and 200 mg/kg, respectively). Particularly, the improving effect of low-dose DCS on each aspect in aged rats was better than high-dose ones.Conclusion: Activation of NMDAR-NMNAT1/2 signaling pathway could not only reduce neuronal apoptosis, but also alleviate sevoflurane-induced neuronal inflammation and cognitive impairment in aged rats.

Hyperbilirubinemia Induces Pro-Apoptotic Effects and Aggravates Renal Ischemia Reperfusion Injury.

AIMS: Hyperbilirubinemia is associated with postoperative acute kidney injury in patients undergoing cardiac surgeries. A high concentration of bilirubin could induce oxidative stress and cell apoptosis. The aim of this study was to investigate whether hyperbilirubinemia aggravated the renal tubule cells injury and the pro-apoptotic potential of bilirubin on renal ischemia reperfusion injury (RIRI). METHODS: The human proximal tubular epithelial cell line HK-2 cells were challenged with a gradient concentration of bilirubin for 24 h. Cell injury was assessed by flow cytometry and MTT assay. Bilirubin was injected intraperitoneally into male Sprague-Dawley rats once every 12 h (100 mg/kg), 3 times in total. The same solvent volume without bilirubin powder was used as vehicle in non-bilirubin injection groups. The RIRI surgical procedure was a bilateral renal pedicles clamping (45 min) followed by 30 h reperfusion. The rats were divided into 4 groups: negative control (NC), similar surgical procedures without clamping; Bil, bilirubin injection for 36 h, then rats were sacrificed; RIRI, RIRI surgical procedures; Bil + RIRI, RIRI applied 6 h later than the first bilirubin injection, rats were sacrificed after another 30 h. RESULTS: In vitro, bilirubin induced cell apoptosis and significantly decreased the cell viability of HK-2 cells. Bilirubin induced the active caspase 3 and phosphorylation of p38 in HK-2 cells. In vivo, serum creatinine was higher in Bil + RIRI compared with RIRI (p < 0.01). The tubular injury scores of hematoxylin and eosin and tubular necrosis scores of periodic acid-Schiff were higher in Bil + RIRI than these in RIRI (All p < 0.05). The number of Tunel-positive nuclei was higher in Bil + RIRI compared to RIRI (p < 0.001). The active caspase 3 and phosphorylation of p38 were higher and the Bcl2 was lower in Bil + RIRI compared to RIRI. Moreover, the apoptosis level was higher in Bil compared to NC. CONCLUSIONS: Our results reveal that the hyperbilirubinemia induces pro-apoptotic effects and aggravates RIRI.

Analgesic effect of TAK-242 on neuropathic pain in rats.

BACKGROUND: The current study investigated the analgesic effect of the Toll-like receptor 4 (TLR4) specific antagonist TAK-242 on neuropathic pain in rats and its underlying mechanism. METHODS: A total of 132 adult Sprague-Dawley (SD) rats were randomly divided into four groups: the sham operation group, the neuropathic pain model group, the TAK-242 low-dose treatment group, and the TAK-242 high-dose treatment group. The heat pain and mechanic pain thresholds of rats were detected on preoperative day 1 and postoperative days 1, 3, 7, and 10. The expression levels of IκBα, p65, IL-1ß, and TNF-α in the spinal cord dorsal horn were detected on postoperative day 7 in one group of rats. RESULTS: Compared with rats in the sham operation group, the heat pain and mechanic pain thresholds of the rats in the neuropathic pain model group significantly decreased; their expression levels of p65, IL-1ß, and TNF-α significantly increased; and their expression level of IkBα significantly decreased. Compared with the neuropathic pain group, high doses of TAK-242 significantly inhibited the expression of p65, IL-1ß, and TNF-α; significantly increased the expression level of IkBα; and upregulated the heat pain and mechanic pain thresholds. CONCLUSION: TAK-242 might improve neuropathic pain through downregulation of the NF-κB pathway.