Sufentanil Improves the Analgesia Effect of Continuous Femoral Nerve Block After Total Knee Arthroplasty.

Purpose: We examined whether the addition of sufentanil to local anesthetics improves the quality of continuous femoral nerve block in patients undergoing total knee arthroplasty (TKA). Patients and Methods: With institutional ethical approval and having obtained written informed consent from each, 35 patients scheduled for elective bilateral TKA with ASA I or II physical status were studied. Bilateral femoral perineural catheters were preoperatively inserted. Both-sided catheters were randomly assigned to receive perineural ropivacaine of 0.2% plus 0.5µg/mL sufentanil deemed as RS group or 0.2% ropivacaine alone deemed as R group at the end of surgery. Visual analogue pain scores (VAS) during activity and at rest of each lower limb were recorded at 6,12,18,24,30,36,42 and 48h after surgery. During the first 48 postoperative hours, the number and reason of patients sleep interruption at night, the number of painful compressions, patient satisfaction and morphine requirements were recorded for each lower limb of patients. Results: Pain scores of RS group on movement were significantly lower than R group, but no difference was noted at rest. When compared to R group, RS group had a lower incidence of sleep interruption at night, fewer painful compressions, higher satisfaction scores and less morphine requirement. Conclusion: The addition of sufentanil to ropivacaine improved analgesia quality of continuous femoral nerve block after arthroplasty.

Tenecteplase vs. Alteplase for Intravenous Thrombolytic Therapy of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: In recent years, as one of the drugs for the treatment of acute ischemic stroke (AIS), the clinical application of tenecteplase is still controversial. Therefore, we aimed to evaluate the safety and efficacy of tenecteplase versus alteplase to guide clinical practice. METHODS: A search of PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023 was conducted to identify eligible articles. The quality of the included studies was assessed using the Cochrane Risk of Bias tool. RevMan 5.3 and Stata 17 were used to perform the meta-analysis and detect publication bias, and risk ratios (RRs) with 95% confidence intervals (95% CIs) were reported for each outcome measure. RESULTS: A total of 1326 records were retrieved in this meta-analysis. As a result of the limited reports on tenecteplase in patients with AIS and the lack of high-quality randomized controlled trials (RCTs), and considering the impact of publication bias, we did not include any of these studies published before 2015. Ultimately we included 16 RCTs with a total of 7508 patients, including 3940 patients treated with alteplase and 3568 patients treated with tenecteplase. Tenecteplase was associated with better early neurological improvement (RR 0.10; 95% CI 0.00-0.19; P = 0.04), recanalization of blood vessels (RR 0.24; 95% CI 0.07-0.40; P = 0.01), and 90-day excellent neurological recovery (RR 0.12; 95% CI 0.01-0.24; P = 0.04). In addition, there were no significant differences in other efficacy and safety outcomes between the two groups. The funnel plot and Begg's as well as Egger's tests showed no significant publication bias. CONCLUSIONS: This meta-analysis showed that tenecteplase was not inferior to alteplase in early thrombolytic therapy in patients with AIS, and was even better than alteplase on some efficacy outcomes with no significant differences in safety. However, as a result of some inherent limitations of this study, more high-quality prospective clinical studies are needed to confirm these results.

In recent years, there has been controversy surrounding the use of tenecteplase, a drug for treating acute ischemic stroke (AIS). To help doctors make better decisions, we compared the safety and effectiveness of tenecteplase with another drug called alteplase. We looked at various research articles from PubMed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases until February 15, 2023. After careful analysis, we found 16 relevant studies with a total of 7508 patients, including those treated with alteplase and tenecteplase. Our findings showed that tenecteplase was as effective as alteplase in providing early thrombolytic therapy for patients with AIS. In fact, tenecteplase even showed better results in some aspects of treatment, without compromising safety. However, we acknowledge some limitations in our study and recommend more high-quality clinical studies to validate these results.

Dexmedetomidine prolongs the duration of local anesthetics when used as an adjuvant through both perineural and systemic mechanisms: a prospective randomized double-blinded trial.

BACKGROUND: To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. METHODS: Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. RESULTS: Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P < 0.001), while it was similar in the DexIV and the control group. For cutaneous territories targeted by the three mid-forearm blocks, the between-group differences behaved similarly. For the other cutaneous territories (musculocutaneous and posterior brachial cutaneous nerves), duration of sensory blockade was shorter in the control group than in the two dexmedetomidine groups. For duration of motor blockade, the between-group differences behaved similarly. Both blood pressure and heart rate were reduced in the DexP and the DexIV groups, compared to the control. CONCLUSIONS: Dexmedetomidine used as an adjuvant to regional anesthesia may act mostly though a perineural mechanism, especially for the sensory aspects of anesthesia. A systemic action might however explain other clinical effects. TRIAL REGISTRATION: ChiCTR-IOR-17011149 , date of registration: 16/04/2017.

Glucosamine promotes seizure activity via activation of the PI3K/Akt pathway in epileptic rats.

CONTEXT: Glucosamine is an amino monosaccharide with a small molecular weight and has a protective effect against various neurological diseases including multiple sclerosis and encephalomyelitis. Interestingly, low-dose glucosamine has exhibited anti-epilepsy activity. Recent studies have shown that the activation of the protein kinase B (Akt) signaling pathway may promote epilepsy. Glucosamine can increase the level of Akt phosphorylation in the brain tissue, which may aggravate epilepsy. Hence, we speculate that a higher dose of glucosamine may aggravate epilepsy via AKT signaling. OBJECTIVE: To investigate the effect of glucosamine on the behavior and electrophysiology of epileptic rats through PI3K/Akt pathway. METHODS: Glucose (2.0 g/kg) and glucosamine (0, 0.5, 1.0, and 2.0 g/kg) were added to 2 mL of drinking water, respectively. An acute seizure rat model of lithium-pilocarpine and PTZ-kindling were constructed to observe the effects of different doses of glucosamine on epileptic behavior and hippocampal electrical activity. Meanwhile, the changes in Akt were detected by western blot. RESULTS: Epileptic seizures were induced by a single dose of pilocarpine or PTZ and 2.0 g/kg of glucosamine significantly prolonged the duration and severity of epileptic seizures, enhanced hippocampal electrical activity energy density, and increased phosphorylated AKT levels. A glucosamine dose of 2.0 g/kg also significantly increased the total onset energy density. Furthermore, 2.0 g/kg glucosamine facilitated the development of the chronic PTZ-kindling process. CONCLUSIONS: Glucosamine may exacerbate acute and chronic epileptic seizures via activation of the PI3K/Akt pathway in rats with experimental epilepsy.

Effect of Ultrasound-guided Nerve Block With 0.75% Ropivacaine at the Mid-forearm on the Prevalence of Moderate to Severe Pain After Hand Surgery.

PURPOSE: This study tested the hypothesis that ultrasound-guided mid-forearm nerve block with 0.75% ropivacaine reduces the prevalence of moderate to severe pain after wrist and hand surgery, and provides prolonged postoperative analgesia with minimal motor blockade. METHODS: Thirty patients undergoing elective wrist and hand surgery were randomly assigned to 1 of 2 groups: group R (n = 15) and group NS (n = 15). We combined an ultrasound-guided supraclavicular brachial plexus block with mid-forearm median, radial, and ulnar nerve block in all patients. The supraclavicular brachial plexus was blocked with 20 mL of 1.5% lidocaine, and the mid-forearm nerves were blocked with 15 mL of either 0.75% ropivacaine (group R) or normal saline (5 mL each nerve) (group NS). A blinded observer provided a numeric rating pain score at 1, 2, 6, 12, 24, and 48 hours after surgery. The durations of sensory and motor blockade, patient satisfaction, morphine requirement for postoperative pain rescue, and adverse events were recorded. FINDINGS: The prevalence of moderate to severe pain in group R was significantly lower than that in group NS (33% vs 86%; P = 0.008). The highest mean (SD) numeric rating pain score (worst pain) in group R was lower than that in group NS (2.7 [1.9] vs 5.6 [2.9]; P = 0.004), and the median (Q1, Q3) amount of morphine required for postoperative pain rescue in group R was lower than that in group NS (0 [0, 6] vs 8 [6, 10]; P = 0.001]. Additionally, there were no differences in the durations of motor blockade between the 2 groups. IMPLICATIONS: Based on the findings from this study, ultrasound-guided mid-forearm nerve block with 0.75% ropivacaine significantly reduces the prevalence of moderate to severe pain after wrist and hand surgery, provides long-term postoperative analgesia, and facilitates the return of motor function in the upper limb. Chinese Clinical Trial Registry identifier: ChiCTR-IOR-15007278 (October 2015).

The ED95 of Nalbuphine in Outpatient-Induced Abortion Compared to Equivalent Sufentanil.

This prospective study evaluated the 95% effective dose (ED95 ) of nalbuphine in inhibiting body movement during outpatient-induced abortion and its clinical efficacy versus the equivalent of sufentanil. The study was divided into two parts. For the first part, voluntary first-trimester patients who needed induced abortions were recruited to measure the ED95 of nalbuphine in inhibiting body movement during induced abortion using the sequential method (the Dixon up-and-down method). In the second part, this was a double-blind, randomized study. Sixty cases of first-trimester patients were recruited and were randomly divided into two groups (n = 30), including group N (nalbuphine at the ED95 dose) and group S (sufentanil at an equivalent dose). Propofol was given to both groups as the sedative. The circulation, respiration and body movement of the two groups in surgery were observed. The amount of propofol, the awakening time, the time to leave the hospital and the analgesic effect were recorded. The ED95 of nalbuphine in inhibiting body movement during painless surgical abortion was 0.128 mg/kg (95% confidence intervals 0.098-0.483 mg/kg). Both nalbuphine and the equivalent dose of sufentanil provided a good intraoperative and post-operative analgesic effect in outpatient-induced abortion. However, the post-operative morbidity of dizziness for nalbuphine was less than for sufentanil (p < 0.05), and the awakening time and the time to leave the hospital were significantly shorter than those of sufentanil (p < 0.05). Nalbuphine at 0.128 mg/kg was used in outpatient-induced abortion as an intraoperative and post-operative analgesic and showed a better effect compared with sufentanil.

Supplement of levosimendan to epinephrine improves initial resuscitation outcomes from asphyxial cardiac arrest.

BACKGROUND: Levosimendan exerted favorable effects on the initial outcome in the treatment of ventricular fibrillation cardiac arrest. This study investigated the efficacy of levosimendan in the treatment of asphyxia-induced cardiac arrest in rats. METHODS: Animals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to three treatment groups: epinephrine (10 µg/kg) supplemented with levosimendan (bolus 12 µg/kg and infusion for 1 h, EL group); epinephrine only (10 µg/kg, E group), or levosimendan only (bolus 12 µg/kg and infusion for 1 h, L group). The resuscitation success rate, wet-to-dry ratio of lung, and rate of alveolar and blood gas analysis were recorded. RESULTS: 10 rats in the EL group, 8 in the E group, and 2 in the L group showed an initial return of spontaneous circulation (P < 0.001); among them, 10, 4, and 2 rats survived at the end of a 60-min observation period from each group, respectively (P = 0.001). The coronary perfusion pressure in the EL group was higher than that of either the E or L group (P < 0.05). The lung wet-to-dry weight ratio and rate of damaged alveoli were lower in the EL group than the E group (P < 0.05). CONCLUSIONS: In the early stage of resuscitation for asphyxia-induced cardiac arrest in rats, levosimendan supplemented with epinephrine can significantly increase coronary perfusion pressure, reduce lung injury, and ultimately enhance the survival rate.

Giving Priority to Lipid Administration Can Reduce Lung Injury Caused by Epinephrine in Bupivacaine-Induced Cardiac Depression.

BACKGROUND AND OBJECTIVES: Epinephrine is usually administered in concert with a lipid emulsion during local anesthetic toxicity. However, the timing and role of epinephrine administration in combination with a lipid emulsion remain unclear. Specifically, the temporal association of epinephrine and lipid emulsion administration with related changes in pulmonary vascular pressures that may lead to pulmonary edema and hemorrhage needs to be determined. METHODS: This study consisted of 2 parts, experiments A and B. In experiment A, 24 adult male Sprague-Dawley rats were randomly divided into 3 groups (n = 8) to receive 1 of 3 treatments. All rats were anesthetized with an intraperitoneal injection of chloral hydrate, and anesthesia was maintained by sevoflurane. Each treatment group was initially given an infusion of bupivacaine (15 mg/kg) in order to produce cardiac depression. Group 1 (A-LEN) received a 30% lipid infusion (3 mL/kg) followed by a rapid epinephrine bolus (10 µg/kg), which was then followed by a normal saline infusion (3 mL/kg). Group 2 (A-NEL) first received a normal saline infusion (3 mL/kg) followed by a rapid epinephrine bolus, which was then followed by a 30% lipid emulsion. Group 3 (A-NEN, considered a control group) first received a normal saline infusion (3 mL/kg) followed by a rapid epinephrine bolus (10 µg/kg), which was then followed by another normal saline infusion (3 mL/kg). Lipid and normal saline infusions were administered over 1 minute, whereas epinephrine was injected rapidly. The continuous monitoring of blood pressure, heart rate, pulmonary arterial pressure, and pulmonary venous pressure occurred for 30 minutes. After the 30-minute monitoring period, lung tissue was sampled, and bronchoalveolar lavage fluid was collected. In experiment B, the experimental model and resuscitation protocol were similar to experiment A (B-LEN and B-NEL groups). In this arm of the experiment, bupivacaine concentrations of cardiac tissue were determined after the second minute of normal saline infusion. RESULTS: The A-LEN group produced the best rate pressure product when compared with the A-NEL or A-NEN group (P = 0.045, P = 0.011, respectively). In regard to pulmonary venous pressure, the A-LEN group was lower than the A-NEL or A-NEN group (P = 0.031, P = 0.006, respectively). Animals in the A-NEL and A-NEN groups rapidly developed pulmonary edema after infusion of epinephrine. The wet-to-dry ratio of the lungs in the A-LEN group was lower than that of the lungs in the A-NEL group (P = 0.024).The lung permeability index of the A-LEN group was lower than that of the A-NEL group (P = 0.011). In experiment B, concentrations of bupivacaine in cardiac tissue and plasma of the B-LEN group were lower than those of the B-NEL group (P = 0.001, P = 0.03, respectively). CONCLUSIONS: Giving priority to the administration of a lipid emulsion before the administration of epinephrine can reduce lung injury in bupivacaine-induced cardiac depression in rats.

Influence of overexpression of SOCS2 on cells of DN rat.

OBJECTIVE: To explore the influence and mechanism of overexpression of SOCS2 on diabetic nephropathy (DN) rats and cells. METHODS: STZ was used to induce male SD rats and SOCS2 was injected into left renal vein. Rats were divided into DN group, DN-Ad-null group and DN-Ad-SOCS2 group. Glucose with high and normal concentration was used to culture HBZY-1 cells and then transfect Ad-SOCS2. HG group, HG-Ad-null group, HG-Ad-SOCS2 group, CG group, CG-Ad-null group, and CG-Ad-SOCS2 group were created. The expression of inflammatory cytokines (MCP-1, TNF-α and IL-6) in kidney tissue of rats, fibrosis related protein (FN, Collagen IV and TGF-ß) in kidney tissue and cells of rats, and JAK/STAT signaling pathway related proteins (p-JAK2 and p-STAT3) were tested by western blot. ELISA was used to test the expression of inflammatory cytokines (TNF-α and IL-6) in cells. RESULTS: The expression of inflammatory cytokines in DN rats (MCP-1, TNF-α and IL-6) and cell (TNF-α and IL-6) were increased (P < 0.01) significantly. However, SOCS2 could decrease the overexpression of mediated inflammatory cytokines in DN animal models and cell models (P < 0.01). The expression of fibrosis related protein in DN rats and cells increased while SOCS2 decreased the overexpression of mediated fibrosis related protein in DN model rats and cells (P < 0.01). The expression of JAK/STAT pathway related protein in both DN rats and cells increased and the JAK/STAT signaling pathway was activated. Yet, SOCS2 obviously suppressed the expression of the JAK/STAT signaling pathway as well as the related proteins (p-JAK2 and p-STAT3) in both DN rats and cells. CONCLUSIONS: The overexpression of SOCS2 can decrease the expression of inflammatory cytokines and fibrosis related proteins in DN rats and cells, and meanwhile suppress the activation of JAK/STAT signaling pathway mediated by DN.