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Item Effect of Esketamine Added to Propofol Sedation on Desaturation and Hypotension in Bidirectional Endoscopy: A Randomized Clinical Trial(American Medical Association, 2023-12-01) Song, Nan; Yang, Yi; Zheng, Zhong; Shi, Wen-Cheng; Tan, Ai-Ping; Shan, Xi-Sheng; Liu, Hong; Meng, Lingzhong; Peng, Ke; Ji, Fu-Hai; Anesthesia, School of MedicineImportance: Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events. Objective: To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy. Design, setting, and participants: This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo). Interventions: After induction of sedation with 0.1 μg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration. Main outcomes and measures: The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction. Results: Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, -12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, -58.9 mg; 95% CI, -65.7 to -52.2 mg; q < .001), without significant effects on other secondary outcomes. Conclusions and relevance: In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures.Item Effects of somatic treatments on suicidal ideation and completed suicides(Wiley, 2021-11) Hawkins, Elise M.; Coryell, William; Leung, Stephen; Parikh, Sagar V.; Weston, Cody; Nestadt, Paul; Nurnberger, John I., Jr.; Kaplin, Adam; Kumar, Anupama; Farooqui, Ali A.; El-Mallakh, Rif S.; Psychiatry, School of MedicineObjective: This work was undertaken to define and characterize the role of currently available somatic treatments in psychiatry in either increasing or reducing the risk for suicide. Methods: Members of the Suicide Prevention Task Group of the National Network of Depression Centers performed a literature review of somatic treatments known to increase or reduce the risk for suicide. The reviews ventured to include all relevant information about the risk for both suicide ideation and completed suicides. Results: Lithium and clozapine are the only two somatic treatments that have high-quality data documenting their antisuicide effects in mood disorders and schizophrenia, respectively. Lithium discontinuation is also associated with increased suicide risk. Ketamine and esketamine may have a small, but immediate, antisuicide effect. Despite the recent Food and Drug Administration approval of esketamine use in depressed suicidal patients, the small disproportional overrepresentation of suicide in subjects who had received esketamine versus placebo (3 vs. 0 among > 3500 subjects) requires ongoing evaluation. The purported antisuicide effect of electroconvulsive therapy is based on low-quality data. The effect of antidepressants is not at all clear. There appears to be direct evidence for antidepressants increasing suicidal ideation and the risk for suicide over the short-term in young people, but indirect (low quality) evidence that antidepressants reduce suicide risk over the long term. Conclusions: Clinicians have an expanding pharmacopeia to address suicide potential in their patients. Some of the agents with documented antisuicide effects may also increase suicidality under specific circumstances.Item Prevention of emergence agitation in seven children receiving low-dose ketamine and propofol total intravenous anesthesia(American Association of Nurse Anesthetists, 2011-06) Anghelescu, Doralina L.; Shearer, Jack; Bikhazi, George B.; Department of Medicine, IU School of MedicineEmergence agitation (EA) can be a distressing side effect of pediatric anesthesia. We observed no recurrence of EA after a low-dose ketamine infusion was added to propofol total intravenous anesthesia in a series of seven pediatric oncology patients repetitively anesthetized for radiation therapy. EA had been documented in all seven patients but did not recur in any of 122 subsequent anesthetics in which this technique was used. Based on these findings, we recommend the addition of low-dose ketamine to propofol infusions for total intravenous anesthesia in order to prevent EA in children with a history of EA.Item Propofol-Based Procedural Sedation with or without Low-Dose Ketamine in Children(Thieme, 2016-03) Ahmed, Sheikh Sohail; Nitu, Mara; Hicks, Shawn; Hedlund, Lauren; Slaven, James E.; Rigby, Mark R.; Biostatistics, School of Public HealthObjective Examine comparative dosing, efficacy, and safety of propofol alone or with an initial, subdissociative dose of ketamine approach for deep sedation. Background Propofol is a sedative-hypnotic agent used increasingly in children for deep sedation. As a nonanalgesic agent, use in procedures (e.g., bone marrow biopsies/aspirations, renal biopsies) is debated. Our intensivist procedural sedation team sedates using one of two protocols: propofol-only (P-O) approach or age-adjusted dose of 0.25 or 0.5 mg/kg intravenous ketamine (K + P) prior to propofol. With either approach, an initial induction dose of 1 mg/kg propofol is recommended and then intermittent dosing throughout the procedure to achieve adequate sedation to safely and effectively perform the procedure. Approach: Retrospective evaluation of 754 patients receiving either the P-O or K + P approach to sedation. Results A total of 372 P-O group patients and 382 K + P group. Mean age (7.3 ± 5.5 years for P-O; 7.3 ± 5.4 years for K + P) and weight (30.09 ± 23.18 kg for P-O; 30.14 ± 24.45 kg for K + P) were similar in both groups (p = NS). All patients successfully completed procedures with a 16% combined incidence of hypoxia (SPO2 < 90%). Procedure time was 3 minutes longer for K + P group than P-O group (18.68 ± 15.13 minutes for K + P; 15.11 ± 12.77 minutes for P-O; p < 0.01), yet recovery times were 5 minutes shorter (17.04 ± 9.36 minutes for K + P; 22.17 ± 12.84 minutes for P-O; p < 0.01). Mean total dose of propofol was significantly greater in P-O than in K + P group (0.28 ± 0.20 mg/kg/min for K + P; 0.40 ± 0.26 mg/kg/min for P-O; p < 0.0001), and might explain the shorter recovery time. Conclusion Both sedation approaches proved to be well tolerated and equally effective. Addition of ketamine was associated with reduction in the recovery time, probably explained by the statistically significant decrease in the propofol dose.Item (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders(MDPI, 2024-06-20) Shafique, Hana; Demers, Julie C.; Biesiada, Julia; Golani, Lalit K.; Cerne, Rok; Smith, Jodi L.; Szostak, Marta; Witkin, Jeffrey M.; Psychology, School of ScienceNMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of (R)-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than (S)-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of (R)-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with (R)-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.