UNASSIGNED: Despite this growing interest, there remains a lack of comprehensive and systematic bibliometric analyses of ketamine research. This study aimed to summarize the progress in ketamine research through bibliometric analysis, providing insights into the development and direction of the field.
UNASSIGNED: Publications related to ketamine were retrieved from the Web of Science Core Collection (WoSCC) database on February 15, 2024. In conducting a comprehensive bibliometric analysis, a variety of bibliographic elements were meticulously collected to map the landscape of research within a specific field.
UNASSIGNED: Between January 1, 2014, and December 31, 2023, a total of 10,328 articles on ketamine research were published across 1,752 academic journals by 45,891 authors from 8,914 institutions in 128 countries. The publication volume has shown a steady increase over this period. The United States of America (USA) and the People\'s Republic of China lead in both publication and citation counts. The National Institute of Mental Health (NIMH) and Yale University emerge as the most active institutions in this research domain. Carlos Zarate of the NIH National Institute of Mental Health was noted for the highest number of significant publications and received the most co-citations. The analysis revealed key research themes including mechanism of action, adverse events, psychiatric applications, and perioperative implications.
UNASSIGNED: This study provided comprehensive bibliometric and knowledge mapping analysis of the global ketamine research landscape, offering valuable insights into the trends, key contributors, and thematic focus areas within the field. By delineating the evolution of ketamine research, this study aims to guide future scholarly endeavors and enhance our understanding of ketamine\'s therapeutic potential.

UNASSIGNED: Incorporating unfamiliar therapies into practice requires effective longitudinal learning and the optimal way to achieve this is debated. Though not a novel therapy, ketamine in critical care has a paucity of data and variable acceptance, with limited research describing intensivist perceptions and utilization. The Coronavirus-19 pandemic presented a particular crisis where providers rapidly adapted analgosedation strategies to achieve prolonged, deep sedation due to a surge of severe acute respiratory distress syndrome (ARDS).
UNASSIGNED: How does clinical experience with ketamine impact the perception and attitude of clinicians toward this therapy?
UNASSIGNED: We conducted a mixed-methods study using quantitative ketamine prescription data and qualitative focus group data. We analyzed prescription patterns of ketamine in a tertiary academic ICU during two different time points: pre-COVID-19 (March 1-June 30, 2019) and during the COVID-19 surge (March 1-June 30, 2020). Two focus groups (FG) of critical care attendings were held, and data were analyzed using the Framework Method for content analysis.
UNASSIGNED: Four-hundred forty-six medical ICU patients were mechanically ventilated (195 pre-COVID-19 and 251 during COVID-19). The COVID-19 population was more likely to receive ketamine (81[32.3%] vs 4 [2.1%], p < 0.001). Thirteen respondents participated across two FG sessions (Pre-COVID = 8, Post-COVID=5). The most prevalent attitude among our respondents was discomfort, with three key themes identified as follows: 1) lack of evidence regarding ketamine, 2) lack of personal experience, and 3) desire for more education and protocols.
UNASSIGNED: Despite a substantial increase in ketamine prescription during COVID-19, intensivists continued to feel discomfort with utilization. Factors contributing to this discomfort include a lack of evidence, a lack of experience, and a desire for more education and protocols. Increase in experience with ketamine alone was not sufficient to minimize provider discomfort. These findings should inform future curricula and call for process improvement to optimize continuing education.

Fear-related disorders, including post-traumatic stress disorder (PTSD), and anxiety disorders are pervasive psychiatric conditions marked by persistent fear, stemming from its dysregulated acquisition and extinction. The primary treatment for these disorders, exposure therapy (ET), relies heavily on fear extinction (FE) principles. Adolescence, a vulnerable period for developing psychiatric disorders, is characterized by neurobiological changes in the fear circuitry, leading to impaired FE and increased susceptibility to relapse following ET. Ketamine, known for relieving anxiety and reducing PTSD symptoms, influences fear-related learning processes and synaptic plasticity across the fear circuitry. Our study aimed to investigate the effects of ketamine (10 mg/kg) on FE in adolescent male C57 BL/6 mice at the behavioral and molecular levels. We analyzed the protein and gene expression of synaptic plasticity markers in the hippocampus (HPC) and prefrontal cortex (PFC) and sought to identify neural correlates associated with ketamine\'s effects on adolescent extinction learning. Ketamine ameliorated FE in the adolescent males, likely affecting the consolidation and/or recall of extinction memory. Ketamine also increased the Akt and mTOR activity and the GluA1 and GluN2A levels in the HPC and upregulated BDNF exon IV mRNA expression in the HPC and PFC of the fear-extinguished mice. Furthermore, ketamine increased the c-Fos expression in specific brain regions, including the ventral HPC (vHPC) and the left infralimbic ventromedial PFC (IL vmPFC). Providing a comprehensive exploration of ketamine\'s mechanisms in adolescent FE, our study suggests that ketamine\'s effects on FE in adolescent males are associated with the activation of hippocampal Akt-mTOR-GluA1 signaling, with the vHPC and the left IL vmPFC as the proposed neural correlates.

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.

NMDA 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.

BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB.
METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction.
RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033).
CONCLUSIONS: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.

UNASSIGNED: This meta-analysis aims to examine how effective ketamine is in the management of acute and preventing chronic post-thoracotomy pain by synthesizing the available research.
UNASSIGNED: A systematic literature search was conducted across PubMed, Scopus, and Cochrane Library till May 2023. Randomized Controlled Trials (RCT) examining the influence of ketamine on post-thoracotomy pain in adults were included. The intervention group included ketamine plus morphine, while the control group included morphine only. The outcome measures were opioid intake and pain scores at rest and on moving/coughing. Evidence quality was evaluated using the Cochrane Risk of Bias and GRADE assessment.
UNASSIGNED: Nine articles comprising 556 patients were selected for meta-analysis. The intervention group had a significant decrease in pain at rest (Std. Mean Difference (SMD = -0.60 with 95% CI [-0.83, -0.37]) and on movement/cough (SMD = -0.73 [-1.27, -0.18]) in the first postoperative days. Also, the ketamine group had lower opioid consumption (mg) in comparison with controls (SMD = -2.75 [-4.14, -1.36], p-value = 0.0001) in postoperative days 1-3. There was no data to assess the long-term effect of ketamine on chronic pain.
UNASSIGNED: This meta-analysis shows that ketamine use can lower acute pain levels and morphine use after thoracotomy. In the future, larger RCTs using standardized methods and assessing both short-term and long-term analgesic effects of ketamine are necessary to deepen the understanding of the issue.

BACKGROUND: An optimal pharmacological strategy for fast-track cardiac anesthesia (FTCA) is unclear. This study evaluated the effectiveness and safety of an FTCA program using methadone and non-opioid adjuvant infusions (magnesium, ketamine, lidocaine, and dexmedetomidine) in patients undergoing coronary artery bypass grafting.
METHODS: This retrospective, multicenter observational study was conducted across private and public teaching sectors. We studied patients managed by a fast-track protocol or via usual care according to clinician preference. The primary outcome was the total mechanical ventilation time in hours adjusted for hospital, body mass index, category of surgical urgency, cardiopulmonary bypass time and EuroSCORE II. Secondary outcomes included successful extubation within four postoperative hours, postoperative pain scores, postoperative opioid requirements, and the development of postoperative complications.
RESULTS: We included 87 patients in the fast-track group and 88 patients in the usual care group. Fast-track patients had a 35% reduction in total ventilation hours compared with usual care patients (p = 0.007). Thirty-five (40.2%) fast-track patients were extubated within four hours compared to 10 (11.4%) usual-care patients (odds ratio: 5.2 [95% CI: 2.39-11.08; p < 0.001]). Over 24 h, fast-track patients had less severe pain (p < 0.001) and required less intravenous morphine equivalent (22.00 mg [15.75:32.50] vs. 38.75 mg [20.50:81.75]; p < 0.001). There were no significant differences observed in postoperative complications or length of hospital stay between the groups.
CONCLUSIONS: Implementing an FTCA protocol using methadone, dexmedetomidine, magnesium, ketamine, lignocaine, and remifentanil together with protocolized weaning from a mechanical ventilation protocol is associated with significantly reduced time to tracheal extubation, improved postoperative analgesia, and reduced opioid use without any adverse safety events. A prospective randomized trial is warranted to further investigate the combined effects of these medications in reducing complications and length of stay in FTCA.
BACKGROUND: The study protocol was registered in the Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au/ACTRN12623000060640.aspx , retrospectively registered on 17/01/2023).

UNASSIGNED: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.
UNASSIGNED: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.
UNASSIGNED: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians.
UNASSIGNED: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks.
UNASSIGNED: Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses.
UNASSIGNED: Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment.
UNASSIGNED: In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

UNASSIGNED: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA).
UNASSIGNED: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine (group ED, n=76), 0.5-μg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications.
UNASSIGNED: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001).
UNASSIGNED: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.
Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.