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Respirology Case Reports May 2024A 70-year-old immunocompetent male with a history of insomnia presented with pneumonia and bacteremia caused by . The patient took benzodiazepines and regularly consumed...
A 70-year-old immunocompetent male with a history of insomnia presented with pneumonia and bacteremia caused by . The patient took benzodiazepines and regularly consumed alcohol and natto (fermented soybeans). Initial antibiotic treatment was not effective, and bronchoalveolar lavage was performed. Bronchoalveolar lavage fluid (BALF) analysis revealed an increased lymphocytes fraction, and was detected in the BALF. Whole-genome sequencing confirmed the congruence of the genetic sequences between the strain in the blood culture of the patient, BALF, and strain isolated from the consumed natto, confirming subsp as the causative pathogen of pneumonia and bacteremia. Vancomycin followed by levofloxacin and systemic corticosteroid were used to treat the condition. This case highlights community-acquired pneumonia and bacteremia caused by subsp, particularly in individuals who consume natto.
PubMed: 38745892
DOI: 10.1002/rcr2.1384 -
BMC Anesthesiology May 2024Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90%... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP).
METHODS
A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded.
RESULTS
A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients.
CONCLUSIONS
A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope.
TRIAL REGISTRATION
The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Male; Female; Hypnotics and Sedatives; Duodenoscopes; Dose-Response Relationship, Drug; Aged; Alfentanil; Middle Aged; Benzodiazepines
PubMed: 38745175
DOI: 10.1186/s12871-024-02554-1 -
Cureus Apr 2024Catatonia is a psychomotor syndrome predominantly associated with mental illness disorders, most commonly bipolar disorder and schizophrenia. Catatonia is classified as...
Catatonia is a psychomotor syndrome predominantly associated with mental illness disorders, most commonly bipolar disorder and schizophrenia. Catatonia is classified as malignant when, in addition to catatonic symptoms, dysautonomia is present. Autonomic abnormalities can include changes in temperature, labile blood pressure, and changes in heart and respiratory rates. Because malignant catatonia is life-threatening, prompt recognition and management are essential to prevent mortality. We present a severe case of catatonia with malignant features that highlight the importance of early diagnosis and treatment.
PubMed: 38741865
DOI: 10.7759/cureus.58142 -
Frontiers in Medicine 2024Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and...
BACKGROUND
Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia, characterised by rapid onset of action, quick recovery, and organ-independent metabolism. Older patients tend to sustain more treatment-emergent adverse events (TEAEs) and worse perioperative prognoses after receiving remimazolam. However, few studies have investigated the appropriate dose of remimazolam for loss of consciousness (LOC) in geriatric patients. We designed this study to provide evidence for dose references and elucidate the relationship between age and remimazolam requirement for inducing LOC during anaesthesia induction.
METHODS
Exactly 120 patients scheduled for general surgery under general anaesthesia were included and divided into two groups: Group A (60 patients, 18-64 years) and Group B (60 patients, ≥ 65 years). LOC, defined as a Modified Observer's Assessment of Alertness and Sedation score at 1 had been reached, emerged after all participants received a continuous infusion of remimazolam at a rate of 0.05 mg/kg/min.
RESULTS
The remimazolam required for inducing LOC was 0.26 and 0.19 mg/kg in groups A and B, respectively, and the remimazolam dose in group B decreased by 26.9% compared to group A. According to the bivariate linear correlation analysis, remimazolam requirement was negatively correlated with age. Multivariable linear regression models and further adjustments for potential impact factors indicated that age was an independent factor for the remimazolam dose required for LOC.
CONCLUSION
This study demonstrated that age was significantly and independently correlated with the remimazolam requirement for inducing LOC. To obtain haemodynamic stability during the induction of general anaesthesia, appropriately reducing the remimazolam dose is recommended for geriatric patients.
PubMed: 38741769
DOI: 10.3389/fmed.2024.1331103 -
PeerJ 2024N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased...
BACKGROUND
N-Ethylmaleimide (NEM), an agonist of the potassium chloride cotransporters 2 (KCC2) receptor, has been correlated with neurosuppressive outcomes, including decreased pain perception and the prevention of epileptic seizures. Nevertheless, its relationship with sleep-inducing effects remains unreported.
OBJECTIVE
The present study aimed to investigate the potential enhancement of NEM on the sleep-inducing properties of alprazolam (Alp).
METHODS
The test of the righting reflex was used to identify the appropriate concentrations of Alp and NEM for inducing sleep-promoting effects in mice. Total sleep duration and sleep quality were evaluated through EEG/EMG analysis. The neural mechanism underlying the sleep-promoting effect was examined through c-fos immunoreactivity in the brain using immunofluorescence. Furthermore, potential CNS-side effects of the combination Alp and NEM were assessed using LABORAS automated home-cage behavioral phenotyping.
RESULTS
Combination administration of Alp (1.84 mg/kg) and NEM (1.0 mg/kg) significantly decreased sleep latency and increased sleep duration in comparison to administering 1.84 mg/kg Alp alone. This effect was characterized by a notable increase in REM duration. The findings from c-fos immunoreactivity indicated that NEM significantly suppressed neuron activation in brain regions associated with wakefulness. Additionally, combination administration of Alp and NEM showed no effects on mouse neural behaviors during automated home cage monitoring.
CONCLUSIONS
This study is the first to propose and demonstrate a combination therapy involving Alp and NEM that not only enhances the hypnotic effect but also mitigates potential CNS side effects, suggesting its potential application in treating insomnia.
Topics: Animals; Alprazolam; Mice; Male; Drug Synergism; Sleep; Electroencephalography; Proto-Oncogene Proteins c-fos; Brain; Reflex, Righting; Hypnotics and Sedatives
PubMed: 38737745
DOI: 10.7717/peerj.17342 -
JGH Open : An Open Access Journal of... May 2024Although no specific sedation recommendations exist in early-stage gastric cancer (ESGC) for endoscopic submucosal dissection (ESD), dexmedetomidine (DEX) is useful...
BACKGROUND AND AIM
Although no specific sedation recommendations exist in early-stage gastric cancer (ESGC) for endoscopic submucosal dissection (ESD), dexmedetomidine (DEX) is useful along with benzodiazepines and analgesics. Furthermore, DEX is used for endoscopic treatment requiring lengthy sedation. However, it is unclear which patients should be administered DEX. We examined the factors that determine when DEX should be added for sedation during ESD for ESGC.
METHODS
Of 316 patients undergoing ESD for ESGC at our hospital between January 2017 and December 2020, we examined 310 receiving intravenous anesthesia. Preoperative patient factors and treatment outcomes were retrospectively examined according to the sedation method.
RESULTS
Among patients with ESGC undergoing ESD at our hospital, DEX was more frequently used alongside sedation in men, those undergoing gastrectomy, those with a lesion diameter ≥20 mm, and those with preoperative ulcers. In the standard group, patients whose treatment duration exceeded 120 min typically had a lesion diameter ≥20 mm, preoperative ulcers, lesions located outside the L region, and were treated by junior physicians.
CONCLUSION
It is important to evaluate specific preoperative factors (lesion diameter ≥20 mm, preoperative ulcers, lesion located outside the L region, and having a junior physician as the treating physician) in patients undergoing ESD for ESGC to determine whether the combined use of DEX in sedation is necessary.
PubMed: 38737500
DOI: 10.1002/jgh3.13065 -
Journal of the Intensive Care Society May 2024Many people survive critical illness with the burden of new or worsened mental health issues and sleep disturbances. We examined the frequency of psychotropic...
BACKGROUND
Many people survive critical illness with the burden of new or worsened mental health issues and sleep disturbances. We examined the frequency of psychotropic prescribing after critical illness, comparing critical care to non-critical care hospitalised survivors, and whether this varied in important subgroups.
METHODS
This retrospective cohort study included 23,340 critical care and 367,185 non-critical care hospitalised adults from 2012 through 2019 in Lothian, Scotland, who survived to discharge.
RESULTS
One-third of critical care survivors (32%; 7527/23,340) received a psychotropic prescription within 90 days after hospital discharge (25% antidepressants; 14% anxiolytics/hypnotics; 4% antipsychotics/mania medicines). In contrast, 15% (54,589/367,185) of non-critical care survivors received a psychotropic prescription (12% antidepressants; 5% anxiolytics/hypnotics; 2% antipsychotics/mania medicines). Among patients without psychotropic prescriptions within 180 days prior to hospitalisation, after hospital discharge, the critical care group had a higher incidence of psychotropic prescription (10.3%; 1610/15,609) compared with the non-critical care group (3.2%; 9743/307,429); unadjusted hazard ratio (HR) 3.39, 95% CI: 3.22-3.57. After adjustment for potential confounders, the risk remained elevated (adjusted HR 2.03, 95% CI: 1.91-2.16), persisted later in follow-up (90-365 days; adjusted HR 1.38, 95% CI: 1.30-1.46), and was more pronounced in those without recorded comorbidities (adjusted HR 3.49, 95% CI: 3.22-3.78).
CONCLUSIONS
Critical care survivors have a higher risk of receiving psychotropic prescriptions than hospitalised patients, with a significant proportion receiving benzodiazepines and other hypnotics. Future research should focus on the requirement for and safety of psychotropic medicines in survivors of critical illness, to help guide policy for clinical practice.
PubMed: 38737305
DOI: 10.1177/17511437231223470 -
The Journal of Medical Investigation :... 2024Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation...
BACKGROUND
Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation and extubation.
CASE REPORT
A 57-year-old man with HAE and a history of laryngeal edema, scheduled to undergo cervical laminoplasty under general anesthesia. General anesthesia was induced by continuous injection of remimazolam and remifentanil, during which manual mask ventilation and intubation were performed without difficulty. The patient was extubated under deep anesthesia. After emergence from general anesthesia, he had no significant upper airway edema and was treated with a C1-inhibitor seven hours post-surgery because of slight tongue swelling. No additional airway edema was observed, and the patient was discharged from the intensive care unit the following day.
CONCLUSIONS
Deep anesthesia tracheal extubation with remimazolam may be effective in preventing upper airway edema during anesthetic management in patients with HAE. J. Med. Invest. 71 : 184-186, February, 2024.
Topics: Humans; Male; Middle Aged; Angioedemas, Hereditary; Anesthesia, General; Benzodiazepines
PubMed: 38735719
DOI: 10.2152/jmi.71.184 -
Molecules (Basel, Switzerland) Apr 2024Two series, "" and "", each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their...
Two series, "" and "", each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABA receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABA receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABA receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, - and -, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the "" series, particularly for compound .
Topics: Anticonvulsants; Animals; Mice; Seizures; Receptors, GABA-A; Pentylenetetrazole; Quinazolinones; Molecular Docking Simulation; Male; Structure-Activity Relationship; Molecular Dynamics Simulation; Computer Simulation; Disease Models, Animal; Molecular Structure; Allosteric Site
PubMed: 38731442
DOI: 10.3390/molecules29091951 -
Journal of Pharmaceutical and... Apr 2024New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their...
New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices. Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10 ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments. The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques. The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification.
PubMed: 38728951
DOI: 10.1016/j.jpba.2024.116175