-
Journal of Anesthesia Aug 2023Anesthesia maintenance using propofol and a propofol bolus dose at the end of surgery have been shown to prevent emergence agitation (EA). However, the preventive...
PURPOSE
Anesthesia maintenance using propofol and a propofol bolus dose at the end of surgery have been shown to prevent emergence agitation (EA). However, the preventive effect of subanesthetic propofol infusion during sevoflurane anesthesia on EA remains unknown. We aimed to evaluate the effect of subanesthetic propofol infusion on EA in children.
METHODS
We retrospectively compared the incidences of severe EA requiring pharmacological intervention in children who underwent adenoidectomy, tonsillectomy with or without adenoidectomy, or strabismus surgery between maintenance with sevoflurane alone (sevoflurane group) and maintenance with subanesthetic propofol with sevoflurane (combination group). A multivariable logistic regression model adjusted for confounders was used to assess the association between anesthesia methods and the occurrence of EA. Additionally, we estimated the direct effect of anesthesia methods by a mediation analysis, excluding the indirect effects of intraoperative fentanyl and droperidol administration.
RESULTS
Among 244 eligible patients, 132 and 112 were in the sevoflurane and combination groups, respectively. The crude incidence of EA was significantly lower in the combination group (17.0% [n = 19]) than in the sevoflurane group (33.3% [n = 44]) (P = 0.005). After adjusting for confounders, the incidence of EA was still significantly lower in the combination group (adjusted odds ratio [aOR]: 0.48, 95% confidence interval [CI] 0.25-0.91). The mediation analysis revealed a direct association of anesthesia methods with a lower EA incidence in the combination group (aOR: 0.48, 95% CI 0.24-0.93) than in the sevoflurane group.
CONCLUSION
Subanesthetic propofol infusion may effectively prevent severe EA requiring the administration of opioids or sedatives.
PubMed: 37188963
DOI: 10.1007/s00540-023-03201-8 -
Anaesthesiology Intensive Therapy 2023
Topics: Humans; Droperidol; Metoclopramide; Neuroleptic Malignant Syndrome; Antiemetics; Postoperative Complications; Rhabdomyolysis; Double-Blind Method
PubMed: 38084576
DOI: 10.5114/ait.2023.132910 -
Journal of Molecular Graphics &... Dec 2023The complex nature of Alzheimer's disease (AD) makes it difficult to understand the exact molecular processes leading to neuron death. However, two molecular factors -... (Meta-Analysis)
Meta-Analysis
Ab initio and comparative 3D modeling of FAM222A-encoded protein and target-driven-based virtual screening for the identification of novel therapeutics against Alzheimer's disease.
The complex nature of Alzheimer's disease (AD) makes it difficult to understand the exact molecular processes leading to neuron death. However, two molecular factors - the production of amyloid-beta plaques and tau tangles - are considered to be linked to AD. A genetic marker for brain atrophy, FAM222A, has been identified by the unique cross-phenotype meta-analysis of genetics imaging and the molecular features show an interaction between the protein aggregatin encoded by FAM222A and amyloid beta (Aβ)-peptide (1-42) via its N-terminal Aβ binding domain, thus increasing Aβ aggregation. Function of Aggregatin protein is unclear, and its 3D structure has not been investigated in experimental analysis, so far. Hence, in the present study, first time in literature, 3D models of FAM222A-encoded Aggregatin were systematically constructed by applying diverse homology modeling approaches and they were used as target structures at the virtual screening of FDA-approved drugs and drugs currently under research in clinical trials. Then, the identified hit molecules were chosen for further molecular dynamics (MD) simulations and post-MD analyses. Our integrated ligand-based and protein-driven-based virtual screening results show that Cefpiramide, Diniprofylline, Fostriecin, and Droperidol may target Aggregatin.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Molecular Dynamics Simulation
PubMed: 37552909
DOI: 10.1016/j.jmgm.2023.108575 -
Academic Emergency Medicine : Official... May 2024The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the...
Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department.
The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE-4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE-4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence].
Topics: Humans; Emergency Service, Hospital; Alcoholism; Vomiting; Adult; Substance Withdrawal Syndrome; Cannabinoids; Benzodiazepines; Syndrome; Marijuana Abuse; Male; Female; Cannabinoid Hyperemesis Syndrome
PubMed: 38747203
DOI: 10.1111/acem.14911 -
Academic Emergency Medicine : Official... Apr 2021The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and safety of intramuscular droperidol, ziprasidone, and lorazepam for acute agitation in the ED.
METHODS
This was a randomized, double-blind trial of ED patients with acute agitation requiring parenteral sedation. The study was conducted under exception from informed consent (21 CFR 50.24) from July 2004 to March 2005. Patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. We recorded Altered Mental Status Scale (AMSS) scores, nasal end-tidal carbon dioxide (ETCO ), and pulse oximetry (SpO ) at 0, 15, 30, 45, 60, 90, and 120 minutes as well as QTc durations and dysrhythmias. Respiratory depression was defined as a change in ETCO consistent with respiratory depression or SpO < 90%. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes.
RESULTS
We enrolled 115 patients. Baseline AMSS scores were similar between groups. For the primary outcome, adequate sedation at 15 minutes, droperidol administration was effective in 16 of 25 (64%) patients, compared to seven of 28 (25%) for 10 mg of ziprasidone, 11 of 31 (35%) for 20 mg of ziprasidone, and nine of 31 (29%) for lorazepam. Pairwise comparisons revealed that droperidol was more effective that the other medications, with 39% (95% confidence interval [CI] = 3% to 54%) more compared to 20 mg of ziprasidone and 33% (95% CI = 8% to 58%) more compared to lorazepam. There was no significant difference between groups in need of additional rescue sedation. Numerically, respiratory depression was lower with droperidol (3/25 [12%]) compared to 10 mg of ziprasidone (10/28 [36%]), 20 mg of ziprasidone (12/31 [39%]), or lorazepam (15/31 [48%]). One patient receiving 20 mg of ziprasidone required intubation to manage an acute subdural hematoma. No patients had ventricular dysrhythmias. QTc durations were similar in all groups.
CONCLUSIONS
Droperidol was more effective than lorazepam or either dose of ziprasidone for the treatment of acute agitation in the ED and caused fewer episodes of respiratory depression.
Topics: Antipsychotic Agents; Droperidol; Emergency Service, Hospital; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Lorazepam; Piperazines; Psychomotor Agitation; Thiazoles
PubMed: 32888340
DOI: 10.1111/acem.14124 -
Biomolecules Jun 2024The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene...
The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene regulation remain elusive. In our study, for the first time, bulk RNA-seq and single-cell RNA-seq data were used to explore the shared molecular mechanisms between T2DM and CRC. Moreover, Connectivity Map and molecular docking were employed to determine potential drugs targeting the candidate targets. Eight genes (, , , , , , , ) were identified as characteristic comorbidity genes for T2DM and CRC, with and further identified as core comorbidity genes. Our results demonstrated that upregulation of EVPL and downregulation of ENTPD3 were intrinsic molecular features throughout T2DM and CRC and were significantly associated with immune responses, immune processes, and abnormal immune landscapes in both diseases. Single-cell analysis highlighted a cancer-associated fibroblast (CAF) subset that specifically expressed ENTPD3 in CRC, which exhibited high heterogeneity and unique tumor-suppressive features that were completely different from classical cancer-promoting CAFs. Furthermore, ENTPD3 CAFs could notably predict immunotherapy response in CRC, holding promise to be an immunotherapy biomarker at the single-cell level. Finally, we identified that droperidol may be a novel drug simultaneously targeting EVPL and ENTPD3. In conclusion, previous studies have often focused solely on metabolic alterations common to T2DM and CRC. Our study establishes EVPL and ENTPD3 as characteristic molecules and immune biomarkers of comorbidity in T2DM and CRC patients, and emphasizes the importance of considering immunological mechanisms in the co-development of T2DM and CRC.
Topics: Humans; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Single-Cell Analysis; Comorbidity; Gene Expression Regulation, Neoplastic; Molecular Docking Simulation; Male
PubMed: 38927096
DOI: 10.3390/biom14060693 -
BMJ Open Mar 2023Acute severe behavioural disturbance (ASBD) is a condition seen with increasing frequency in emergency departments (EDs) in adults and young people. Despite the...
INTRODUCTION
Acute severe behavioural disturbance (ASBD) is a condition seen with increasing frequency in emergency departments (EDs) in adults and young people. Despite the increasing number of presentations and significant associated risks to patients, families and caregivers, there is limited evidence to guide the most effective pharmacological management in children and adolescents. The aim of this study is to determine whether a single dose of intramuscular olanzapine is more effective than intramuscular droperidol at successfully sedating young people with ASBD requiring intramuscular sedation.
METHODS AND ANALYSIS
This study is a multicentre, open-label, superiority randomised controlled trial. Young people aged between 9 and 17 years and 364 days presenting to an ED with ASBD who are deemed to require medication for behavioural containment will be recruited to the study. Participants will be randomised in a 1:1 allocation between a single weight-based dose of intramuscular olanzapine and intramuscular droperidol. The primary outcome is the proportion of participants who achieve successful sedation at 1-hour post randomisation without the need for additional sedation. Secondary outcomes will include assessing for adverse events, additional medications provided in the ED, further episodes of ASBD, length of stay in the ED and hospital and satisfaction with management.Effectiveness will be determined using an intention-to-treat analysis, with medication efficacy determined as part of the secondary outcomes using a per-protocol analysis. The primary outcome of successful sedation at 1 hour will be presented as a percentage within each treatment group, with comparisons presented as a risk difference with its 95% CIs.
ETHICS AND DISSEMINATION
Ethics approval was received from the Royal Children's Hospital Human Research Ethics Committee (HREC/69948/RCHM-2021). This incorporated a waiver of informed consent for the study. The findings will be disseminated in a peer-reviewed journal and at academic conferences.
TRIAL REGISTRATION NUMBER
ACTRN12621001238864.
Topics: Adult; Adolescent; Humans; Child; Infant, Newborn; Droperidol; Prunus persica; Olanzapine; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 36997241
DOI: 10.1136/bmjopen-2022-067436 -
Journal of Clinical PsychopharmacologyDroperidol is an antipsychotic medication used in psychiatric emergencies to manage acute behavioral disturbance. Droperidol use carries a risk of prolonged QT interval...
PURPOSE/BACKGROUND
Droperidol is an antipsychotic medication used in psychiatric emergencies to manage acute behavioral disturbance. Droperidol use carries a risk of prolonged QT interval on the electrocardiogram and associated cardiac arrhythmias including torsades de pointes and ventricular fibrillation. This study aimed to evaluate the safety of droperidol in adults admitted to the psychiatric inpatient unit of a large Australian hospital.
METHODS/PROCEDURES
In this retrospective cohort study, psychiatric inpatients admitted between October 22, 2018, and March 1, 2021, who received at least 1 dose of intramuscular droperidol were consecutively included. Outcomes of interest were death, cardiac arrhythmias, and QT prolongation. QT prolongation was identified using the QT-interval nomogram.
FINDINGS/RESULTS
This study included 263 patients without exclusion. No deaths or cases of cardiac arrhythmia were recorded within 24 hours of droperidol administration. Electrocardiogram data were available for 41.1% of patients (n = 108) within 7 days of droperidol administration. Two cases of QT prolongation were identified using the QT-interval nomogram, but these patients were also prescribed other medications that may have contributed to QT prolongation.
IMPLICATIONS/CONCLUSIONS
This study contributes the first known large retrospective study of safety outcomes including QT prolongation after droperidol administration in a psychiatric inpatient setting. Our findings corroborate mounting evidence supporting the clinical safety of droperidol use in psychiatric settings. Nonetheless, we note that significant barriers remain with regard to timely electrocardiogram monitoring after droperidol use.
Topics: Adult; Humans; Droperidol; Inpatients; Retrospective Studies; Australia; Long QT Syndrome; Arrhythmias, Cardiac; Torsades de Pointes; Electrocardiography
PubMed: 37068031
DOI: 10.1097/JCP.0000000000001688 -
Journal of Evidence-based Medicine Sep 2021In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form.
METHODS
We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia.
RESULTS
585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing.
CONCLUSIONS
There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.
Topics: Adult; Anesthesia, General; Antiemetics; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Postoperative Nausea and Vomiting
PubMed: 34043870
DOI: 10.1111/jebm.12429 -
Oncology Letters Aug 2020Preeclampsia (PE) is characterized by gestational hypertension and proteinuria, and is a leading cause of maternal death and perinatal morbidity globally. Although the...
Preeclampsia (PE) is characterized by gestational hypertension and proteinuria, and is a leading cause of maternal death and perinatal morbidity globally. Although the exact cause of PE remains unclear, several studies have suggested a role for abnormal expression of multiple genes. The aim of the present study was to identify key genes and related pathways, and to screen for drugs that regulate these genes for potential PE therapy. The GSE60438 dataset was acquired from the Gene Expression Omnibus database to analyze differentially expressed genes (DEGs). By constructing a protein-protein interaction network and performing reverse transcription-quantitative PCR verification, proteasome 26S subunit, non-ATPase 14, prostaglandin E synthase 3 and ubiquinol-cytochrome reductase core protein 2 were identified as key genes in PE. In addition, PE was found to be associated with 'circadian rhythm', 'fatty acid metabolism', 'DNA damage response detection of DNA damage', 'regulation of DNA repair' and 'endothelial cell development'. Through connectivity map analysis of DEGs, furosemide and droperidol were suggested to be therapeutic drugs that may target the hub genes for PE treatment. Results analysis of GSEA were included in the discussion section of this article. In conclusion, the current study identified novel key genes associated with the onset of PE and potential drugs for PE treatment.
PubMed: 32724400
DOI: 10.3892/ol.2020.11721