Effect of Nalmefene on Delayed Neurocognitive Recovery in Elderly Patients Undergoing Video-assisted Thoracic Surgery with One Lung Ventilation

The intravenous use of nalmefene has been found to exert neuroprotective effect in patients with severe traumatic brain injury and acute cerebral infarction;nonetheless,it is unknown whether nalmefene alleviates delayed neurocognitive recovery.Our purpose of the current research was to clarify the impact of nalmefene on delayed neurocognitive recovery in aged patients experiencing video-assisted thoracic surgery(VATS)with intraoperative use of one lung ventilation(OLV).The present study involved 120 paticents undergoing selective VATS,randomized to accept low-dose nalmefene(N1 group,n=40),high-dose nalmefene(N2 group,1n=40)or equal volume of physiologic saline(control group,1=40).A battery of neuropsychological tests were used to estimate cognitive function I day before surgery(o)and 10 days after surgery or before discharge(t).Regional cerebral oxygen saturation(rSO2)was detected 5 min before induction(t),5 min after induction(1),15 and 60 min after onset of OLV(62 and 13),and 15 min after termination of OLV(4).The plasma values of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-a1 and adiponectin(ADP)were also detected prior to induction of anesthesia(T0),1 h,2 h and 6 h after surgery(TI,T2,T3).On 1,delayed neurocognitive recovery occurred in 5/40(12.5%)patients of NI group,in 5/40(12.5%)patients of N2 group and in 13/40(32.5%)patients of control group(P<0.05).There were no statistical differences in rSO2 among three groups at different time points.At Tl,T2 and T3,IL-1β,IL-6 and TNF-a values significantly increased and ADP value significantly decreased(P<0.05)in control group.In contrast,at TI,T2 and T3,IL-1β,IL-6 and TNF-a values decreased and ADP value decreased less in N1 and N2 groups(P<0.05).At TI,T2 and T3,IL-1β,IL-6 and TNF-a concentrations presented a trend of N2 group<N1 group<control group and ADP presented a trend of N2 group>Nl group>control group(P<0.05).The result of our present research supports the hypothesis that the perioperative intravenous treatment with nalmefene to VATS with OLV ameliorates postoperative cognitive function and decreases the incidence of delayed neurocognitive recovery,most likely by suppression of inflammatory responses.

Efficacy and Tolerability of Long-Acting Injectable Formulation of Nalmefene (Nalmefene Consta 393.1 mg) for Opioid Relapse Prevention: A Multicentre, Open-Label, Randomised Controlled Trial

Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.

美国：遏制“购物狂”

你是购物狂吗？一见心爱的东西就会失控，掏尽一个月的薪水只为一件限量饰品。为了有限遏制这种症状的出现，科学家们研究出一种名叫Nalmefene的药片。