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Drug Design, Development and Therapy 2024To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery.
PATIENTS AND METHODS
141 cases of gynaecological daycase surgery patients in Weifang People's Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded.
RESULTS
The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05).
CONCLUSION
Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.
Topics: Female; Humans; Alfentanil; Ambulatory Surgical Procedures; Antiemetics; Benzodiazepines; Flumazenil; Gynecologic Surgical Procedures; Postoperative Nausea and Vomiting
PubMed: 38465267
DOI: 10.2147/DDDT.S444313 -
Journal of Gastrointestinal and Liver... Jun 2024Mammoplasty, a common cosmetic procedure involving breast augmentation and reduction surgeries, has gained global popularity. Recently, attention has shifted towards...
BACKGROUND AND AIMS
Mammoplasty, a common cosmetic procedure involving breast augmentation and reduction surgeries, has gained global popularity. Recently, attention has shifted towards understanding the prevalence and significance of gastrointestinal (GI) symptoms following mammoplasty. This systematic review aims to consolidate existing literature to provide a comprehensive overview of the type and frequency of GI problems associated with various mammoplasty procedures.
METHODS
A systematic search of PubMed and Scopus databases was conducted until January 22, 2024, identifying observational and interventional studies examining GI symptoms post-mammoplasty. Inclusion criteria covered human studies, while exclusion criteria ensured specificity. Two independent investigators performed screening, and data extraction included study characteristics, surgical procedures, anesthesia methods, and interventions.
RESULTS
Nineteen studies, involving 2,487 subjects, were included in the review. Breast reconstruction emerged as the most studied procedure, followed by breast reduction, augmentation, mastectomy, and breast cancer surgery. Predominant GI symptoms included nausea and vomiting, with varying rates across mammoplasty types. Anesthesia modality influenced symptomatology, with general, local, and combined anesthesia associated with GI disturbances. Antiemetics, notably ondansetron and droperidol, showed variable efficacy. Non-pharmacological approaches, such as preoperative hypnosis, were explored for symptom management.
CONCLUSIONS
Our systematic review reveals insights into GI symptoms post-mammoplasty, emphasizing the common occurrence of symptoms such as nausea and vomiting, alongside less frequent manifestations such as constipation, dry mouth, retching, abdominal pain, and tightness. Variations in symptom prevalence were noted across diverse mammoplasty surgeries, anesthesia methods, and the use of antiemetics, underscoring the complex nature of post-mammoplasty GI disturbances.
Topics: Humans; Mammaplasty; Female; Postoperative Nausea and Vomiting; Gastrointestinal Diseases; Adult; Prevalence
PubMed: 38944853
DOI: 10.15403/jgld-5598 -
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 -
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 -
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 -
Molecular Diversity Oct 2023Acinetobacter baumannii belongs to the ESKAPE family of pathogens and is a multi-drug resistant, gram-negative bacteria which follows the anaerobic form of respiration....
Acinetobacter baumannii belongs to the ESKAPE family of pathogens and is a multi-drug resistant, gram-negative bacteria which follows the anaerobic form of respiration. A. baumannii is known to be the causative agent of hospital-related infections such as pneumonia, meningitis, endocarditis, septicaemia and a plethora of infections such as urinary tract infections found primarily in immunocompromised patients. These attributes of A. baumannii make it a priority pathogen against which potential therapeutic agents need to be developed. A. baumannii employs the formation of a biofilm to insulate its colonies from the outer environment, which allows it to grow under harsh environmental conditions and develop resistance against various drug molecules. Acyl-homoserine lactone synthase (AHLS) is an enzyme involved in the quorum-sensing pathway in A. baumannii, which is responsible for the synthesis of signal molecules known as acyl-homoserine lactones, which trigger the signalling pathway to regulate the factors involved in biofilm formation and regulation. The present study utilised a homology-modelled structure of AHLS to virtually screen it against the ZINC in trial/FDA-approved drug molecule library to find a subset of potential lead candidates. These molecules were then filtered based on Lipinski's, toxicological and ADME properties, binding affinity, and interaction patterns to delineate lead molecules. Finally, three promising molecules were selected, and their estimated binding affinity values were corroborated using AutoDock 4.2. The identified molecules and a control molecule were subsequently subjected to MD simulations to mimic the physiological conditions of protein ligand-binding interaction under the influence of a GROMOS forcefield. The global and essential dynamics analyses and MM/PBSA based binding free energy computations suggested Droperidol and Cipargamin as potential inhibitors against the binding site of AHLS from A. baumannii. The binding free energy calculations based on the MM/PBSA method showed excellent results for Droperidol (- 50.02 ± 4.67 kcal/mol) and Cipargamin (- 42.29 ± 4.05 kcal/mol).
Topics: Humans; Acyl-Butyrolactones; Droperidol; Biofilms; Quorum Sensing
PubMed: 36190592
DOI: 10.1007/s11030-022-10533-2 -
The American Journal of Emergency... Jan 2024Gastroparesis is a syndrome of delayed gastric emptying without obstruction. There are high rates of Emergency Department (ED) visits due to gastroparesis, and this...
BACKGROUND/PURPOSE
Gastroparesis is a syndrome of delayed gastric emptying without obstruction. There are high rates of Emergency Department (ED) visits due to gastroparesis, and this chronic disease is difficult to treat which often leads to hospital admissions. This study aimed to evaluate the impact droperidol administration has on opioid therapy, symptom relief, co-administration of antiemetic and prokinetic medications, disposition, cost, and length of stay (LOS) of patients presenting to the ED.
RESULTS
A total of 431 patients were identified and 233 met the inclusion criteria. Droperidol administration reduced the number of patients requiring opioid therapy (108/233 [46%] vs 139/233 [60%], P-value 0.0040), reduced patient-reported pain scales by 4 points, and reduced antiemetic therapy requirement (140/233 [60%] vs 169/233 [73%], P-value 0.0045). No differences were found in terms of ED LOS (Median 6 h [IQR 4-8] vs 5 h [IQR 4-9], P-value 0.3638), hospital LOS (Median 6 h [IQR 4-30 vs 7 h [IQR 4-40], P-value 0.8888), hospital admission rates (67/233 [29%] vs 71/233 [31%], P-value 0.6101), ED cost to the facility (Median $1462 [IQR $1114 - $1986] vs $1481 [IQR $1034 - $2235], P-value 0.0943), or hospital cost (Median $4412 [IQR $2359 - $9826] vs $4672 [IQR $2075 - $9911], P-value 0.3136).
CONCLUSION
In patients with gastroparesis presenting to the ED, droperidol reduced opioid use, improved pain control, and decreased antiemetic use without any differences in MME per dose, length of stay, hospital admission rate, or cost.
Topics: Humans; Droperidol; Antiemetics; Analgesics, Opioid; Gastroparesis; Length of Stay; Emergency Service, Hospital; Pain; Retrospective Studies
PubMed: 37897920
DOI: 10.1016/j.ajem.2023.10.030 -
Expert Opinion on Drug Metabolism &... Jun 2024Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). (Review)
Review
INTRODUCTION
Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).
AREAS COVERED
Eight D-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.
EXPERT OPINION
Since the introduction of D-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)-RAs and neurokinin (NK)-RAs have been developed. The classical D-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT-RA, dexamethasone and a NK-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.
Topics: Humans; Nausea; Vomiting; Antiemetics; Antineoplastic Agents; Dopamine Antagonists; Animals; Dopamine D2 Receptor Antagonists; Receptors, Dopamine D3
PubMed: 38878283
DOI: 10.1080/17425255.2024.2367593 -
Federal Practitioner : For the Health... Apr 2024Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and...
BACKGROUND
Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and antipsychotics are commonly used for agitation, but safety concerns exist with these medications in older adults, even with acute use. The purpose of this study was to compare prescribing practices of anti-agitation medications between adults aged 18 to 64 years and those aged ≥ 65 years.
METHODS
This study was a retrospective chart review of patients who presented to the Veteran Affairs Southern Nevada Healthcare System emergency department and received haloperidol, droperidol, lorazepam, olanzapine, or ziprasidone from August 1, 2019, to July 31, 2022. Veterans were excluded if they had alcohol intoxication, alcohol withdrawal, benzodiazepine withdrawal, or medication administration unrelated to agitation. Safety outcomes included oxygen saturation < 95%, supplemental oxygen use, intubation, QTc prolongation, and new hypotension within 1 hour of medication administration.
RESULTS
For the 232 patients who met inclusion criteria, baseline characteristics differed significantly. When comparing patients aged 18 to 64 years and those aged ≥ 65 years, the younger cohort had higher rates of substance use disorder diagnosis (55.3% vs 27.5%, < .001), positive urine drug screen (69.7% vs 22.5%, < .001), and 72-hour legal hold (59.9% vs 32.5%, < .001), and lower rates of cognitive impairment or dementia (0.7% vs 48.8%, < .001), and altered mental status-related diagnosis (2.0% vs 18.8%, < .001). Anti-agitation medication selection significantly differed based on age ( = .02). Other than lorazepam ( = .007), no significant differences were noted in the dose ordered. No significant differences were observed for safety outcomes or additional anti-agitation doses.
CONCLUSIONS
Anti-agitation prescribing practices may differ between adults aged 18 to 64 years and those aged ≥ 65 years. The findings of this study also suggest that the most common agitation etiologies may differ based on patient age. Additional higher-quality studies are needed to further explore acute agitation in older adults.
PubMed: 38813266
DOI: 10.12788/fp.0456