Browsing by Subject "Benzodiazepine"

Now showing 1 - 3 of 3
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    Deprescribing in the Pharmacologic Management of Delirium (de-PMD): A Randomized Trial in the Intensive Care Unit
    (Wiley, 2019-04) Campbell, Noll L.; Perkins, Anthony J.; Khan, Babar A.; Gao, Sujuan; Farber, Mark O.; Khan, Sikandar; Wang, Sophia; Boustani, Malaz A.; Medicine, School of Medicine
    OBJECTIVE: Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. DESIGN: Multi-site randomized clinical trial SETTING: ICU’s of three large hospitals PARTICIPANTS: Two hundred adults aged ≥ 18 years admitted to an ICU with delirium according to the Richmond Agitation Severity Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. MEASUREMENTS: Primary outcomes were delirium duration measured by the CAM-ICU, and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. RESULTS: Participants had a mean age of 61.8 (standard deviation: 14.3) years, 59% female, and 52% African American with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (p=0.219) or benzodiazepines (p=0.566), the median total anticholinergic score (p=0.282), or the median total benzodiazepine dose in lorazepam equivalents (p=0.501). Neither median delirium/coma-free days (p=0.361) nor median change in delirium severity scores (p=0.582 for DRS-R-98; p=0.333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. CONCLUSIONS: When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes.
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    The GABA(A) receptor alpha1 subtype in the ventral pallidum regulates alcohol-seeking behaviors
    (Society for Neuroscience, 2002-05-01) Harvey, Scott C.; Foster, Katrina L.; McKay, Pete F.; Carroll, Michelle R.; Seyoum, Regat; Woods, James E., II; Grey, Collette; Jones, Cecily M.; McCane, Shannan; Cummings, Rancia; Mason, Dynesha; Ma, Chunrong; Cook, James M.; June, Harry L.; Psychology, School of Science
    We investigated the potential role of the alpha1-containing GABA(A) receptor in regulating the reinforcing properties of alcohol. To accomplish this, we developed 3-propoxy-beta-carboline hydrochloride (3-PBC), a mixed agonist-antagonist benzodiazepine site ligand with binding selectivity at the alpha1 receptor. We then tested the capacity of 3-PBC to block alcohol-maintained responding in the ventral pallidum (VP), a novel alcohol reward substrate, which primarily expresses the alpha1-receptor isoform. Our results demonstrated that bilateral microinfusion of 3-PBC (0.5-40 microg) in the anterior and medial VP produced marked reductions in alcohol-maintained responding in a genetically selected rodent model of alcohol drinking. The VP infusions showed both neuroanatomical and reinforcer specificity because no effects were seen in sites dorsal to the VP (e.g., nucleus accumbens, caudate putamen). The saccharin-maintained responding was reduced only with the highest dose (40 microg). Parenteral injections of 3-PBC (1-20 mg/kg) also showed a similar selectivity on alcohol-maintained responding. Complementary in vitro studies revealed that 3-PBC exhibited a low partial agonist efficacy profile at recombinant diazepam-sensitive receptors (e.g., alpha1beta3gamma2, alpha2beta3gamma, and alpha3beta3gamma2). The selective suppression of 3-PBC on alcohol-maintained responding after central and parenteral administrations, together with its low-efficacy agonist profile, suggest that the reduction in alcohol-maintained behaviors was not attributable to a general suppression on consummatory behaviors. These results demonstrate that the alpha1-containing GABA(A) receptors in both the anterior and medial VP are important in regulating the reinforcing properties of alcohol. These receptors represent novel targets in the design and development of pharmacotherapies for alcohol-dependent subjects.
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    Pharmacological Management of Delirium in the Intensive Care Unit: A Randomized Pragmatic Clinical Trial
    (Wiley, 2019-05) Khan, Babar A.; Perkins, Anthony J.; Campbell, Noll L.; Gao, Sujuan; Farber, Mark O.; Wang, Sophia; Khan, Sikandar H.; Zarzaur, Ben L.; Boustani, Malaz A.; Biostatistics, School of Public Health
    BACKGROUND/OBJECTIVE: Delirium in the intensive care units (ICUs) is prevalent, with both delirium duration and delirium severity associated with adverse outcomes. We designed a pragmatic trial to test the efficacy of a pharmacological management of delirium (PMD) bundle in improving delirium/coma-free days and reducing delirium severity among ICU patients. DESIGN: A randomized pragmatic clinical trial. SETTING: Medical, surgical, and progressive ICUs of three tertiary care hospitals. PARTICIPANTS: A total of 351 critically ill patients. INTERVENTION: A multicomponent PMD bundle consisting of reducing the exposure to 20 definite anticholinergic medications and benzodiazepines and prescribing low-dose haloperidol. MEASUREMENTS: The primary outcomes were delirium/coma-free days, measured through the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU), and delirium severity, measured through Delirium Rating Scale-Revised-98 and the CAM-ICU-7. Secondary outcomes were in-hospital and posthospital discharge 30-day mortality, ICU and hospital lengths of stay, and delirium-related hospital complications. RESULTS: We randomized 351 critically ill delirious patients (mean age = 59.3 years [SD = 16.9 years]; 52% female, 42% African Americans) to receive the PMD bundle or usual care. There were no significant differences in median delirium/coma-free days at day 8 (PMD vs usual care = 4 [interquartile range {IQR} = 2-7] days vs 5 [IQR = 1-7] days; P = .888) or at day 30 (PMD vs usual care = 26 [IQR 19-29] days vs 26 [IQR, 14-29] days; P = .991). There were no significant differences for decrease in delirium severity at day 8, but at hospital discharge, the intervention group showed a greater reduction in delirium severity (mean decrease in CAM-ICU-7 score for PMD vs usual care = 3.2 [SD = 3.3] vs 2.5 [SD = 3.2]; P = .046). No differences were observed between groups for ICU and hospital lengths of stay, mortality, and delirium-related hospital complications. Similar results were observed when analyses were limited to patients 65 years or older and 75 years or older. CONCLUSION AND RELEVANCE: Implementing the PMD bundle in the ICU did not reduce delirium duration or severity among critically ill patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00842608. J Am Geriatr Soc 67:1057-1065, 2019.