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Academic Emergency Medicine : Official... Jan 2016Olanzapine is an atypical antipsychotic with similar pharmacologic properties to droperidol. Due to the current droperidol shortage, the authors' clinical practice has...
BACKGROUND
Olanzapine is an atypical antipsychotic with similar pharmacologic properties to droperidol. Due to the current droperidol shortage, the authors' clinical practice has been to substitute olanzapine for droperidol in many situations. At this time, olanzapine is U.S. Food and Drug Administration approved for oral and intramuscular (IM) use only, but due to its increased utility, intravenous (IV) olanzapine was recently approved for use in the study emergency department (ED).
OBJECTIVES
The authors sought to review the use and safety of IV olanzapine in the ED patient population.
METHODS
A retrospective review of consecutive patients receiving IV olanzapine between January 1, 2014, and July 1, 2014, was conducted. Data were collected via an electronic medical record review. The study was deemed exempt from informed consent by our institutional review board.
RESULTS
A total of 713 patients received IV olanzapine during the study period. The median age was 38 years (range = 18 to 85 years), and 313 patients were male (43.9%). Primary indications for IV olanzapine administration included acute agitation (n = 245, 34.4%), abdominal pain (n = 165, 23.1%), headache (n = 121, 17.0%), nausea and vomiting (n = 107, 15.0%), pain (other; n = 60, 8.4%), and unknown (n = 15, 2.1%). IV dosing varied: 1.25 mg (n = 20, 2.8%), 2.5 mg (n = 185, 25.9%), 5 mg (n = 507, 71.1%), and 10 mg (n = 1, 0.1%). Forty-nine patients required a second dose of olanzapine (22 IV, 26 IM, one oral). The maximum total dose of olanzapine was 20 mg. Ninety-eight patients required a total of 146 doses of additional sedatives during their ED course. Other sedative medications included ketamine (n = 17, 2.4%), haloperidol (n = 48, 6.7%), and benzodiazepines (n = 81, 11.4%). Hypoxia was noted in 74 patients (10.4%). Major respiratory complications, including airway stimulation or repositioning maneuvers and intubation, occurred in 15 patients (2.1%). After consensus review, one intubation was classified as "likely related" to olanzapine administration, and two were classified as "possibly related" to olanzapine. Akathisia likely occurred in four patients (0.6%), and no allergic reactions were identified. Electrocardiograms (ECGs) were performed in 322 patients. A total of 251 patients had an ECG performed before olanzapine administration (median QTc = 404 ms), and 88 patients had an ECG performed after olanzapine administration (median QTc = 415 ms). Acute alcohol and drug intoxication was common, 118 (16.5%) patients were positive for ethanol, and seven of 23 drug screens were positive for sympathomimetics. Thirty-four of 284 admissions (4.5%) were to intermediate or intensive care unit beds. No patients died while in the ED and no cases of sudden cardiac death were noted.
CONCLUSIONS
In this large retrospective review, IV olanzapine appears to be a safe in the management of a variety of ED indications. Hypoxia was common, but serious airway compromise was rare.
Topics: Administration, Intravenous; Adult; Antipsychotic Agents; Benzodiazepines; Droperidol; Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pain; Psychomotor Agitation; Retrospective Studies; United States; Young Adult
PubMed: 26720055
DOI: 10.1111/acem.12842 -
Medicine Jun 2016The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be... (Randomized Controlled Trial)
Randomized Controlled Trial
The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be combined in PCA solutions. The combination of analgesics and antiemetic agents is frequently required. Unfortunately, the compatibility and stability of lornoxicam and antiemetic agents, such as droperidol, ondansetrone, granisetron, and tropisetron, has not been determined. The aim of this study was to evaluate the compatibility and stability of solutions containing lornoxicam with the 4 antiemetic agents in combination for PCA administration.In our study, test samples were prepared in triplicate by adding 40 mg lornoxicam and 5 mg droperidol, 8 mg ondansetron, 6 mg granisetron, or 5 mg tropisetron to 100-mL polyolefin bags of sodium chloride 0.9% and stored at 25 °C. The analgesic mixture samples were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using high-performance liquid chromatographic (HPLC) analysis.No loss of lornoxicam occurred with any of the 4 antiemetic agents tested for up to 48 hours. However, the contents of droperidol, ondansetron, granisetron, and tropisetron were significant loss >48 hours. After storage of 4.0 to 48.0 hours, the presence of a slight precipitate was observed in all the injection combinations.The results indicate that combinations of lornoxicam with droperidol, ondansetrone, granisetron, or tropisetron in infusion solution during simulated intravenous PCA administration were incompatibility when stored protected from light at 25 °C.
Topics: Analgesia, Patient-Controlled; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Drug Incompatibility; Drug Stability; Drug Storage; Drug Therapy, Combination; Humans; Infusions, Intravenous; Pain, Postoperative; Patient Simulation; Piroxicam; Polyenes
PubMed: 27336868
DOI: 10.1097/MD.0000000000003824 -
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 -
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 -
British Journal of Anaesthesia Jun 2017: The combination of dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) is efficacious in preventing postoperative nausea and vomiting in adults, but has not... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
: The combination of dexamethasone (DEX), ondansetron (OND) and droperidol (DRO) is efficacious in preventing postoperative nausea and vomiting in adults, but has not been well assessed in children.
METHODS
: Children undergoing elective surgery under general anaesthesia and considered at high risk for postoperative vomiting (POV) were randomly assigned to receive a combination of DEX, OND and placebo (Group A) or a combination of DEX, OND and DRO (Group B). The primary outcome was the incidence of POV during the first 24 hours after surgery. We hypothesized that the addition of DRO to the standard antiemetic prophylaxis would provide a further 15% reduction in the residual risk for POV. The secondary outcome considered was any adverse event occurring during the study.
RESULTS
: One hundred and fifty-three children, aged three to 16 years, were randomized to Group A and 162 to Group B. The overall incidence of POV did not differ significantly between the two groups, with 16 patients in Group A (10.5%) and 18 in Group B (11.1%) presenting with one or more episodes of POV, P =0.86. Fewer patients presented with adverse events in Group A (2%) compared with Group B (8%), P =0.01. Drowsiness and headache were the principal adverse events reported.
CONCLUSIONS
: The addition of DRO to a combination of OND and DEX did not decrease POV frequency below that obtained with the two-drug combination in children at high risk of POV, but increased the risk of drowsiness. The combination of DEX and OND should be recommended in children with a high risk of POV.
CLINICAL TRIAL REGISTRATION.
NCT01739985.
Topics: Adolescent; Anesthesia, General; Antiemetics; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Droperidol; Drug Therapy, Combination; Elective Surgical Procedures; Female; Humans; Incidence; Male; Ondansetron; Postoperative Nausea and Vomiting
PubMed: 28505233
DOI: 10.1093/bja/aex099 -
International Journal of Molecular... Apr 2019Dopamine D₂ receptors (D₂R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of...
Dopamine D₂ receptors (D₂R) are known to form transient homodimer complexes, of which the increased formation has already been associated with development of schizophrenia. Pharmacological targeting and modulation of the equilibrium of these receptor homodimers might lead to a better understanding of the critical role played by these complexes in physiological and pathological conditions. Whereas agonist addition has shown to prolong the D₂R dimer lifetime and increase the level of dimer formation, the possible influence of D₂R antagonists on dimerization has remained rather unexplored. Here, using a live-cell reporter assay based on the functional complementation of a split Nanoluciferase, a panel of six D₂R antagonists were screened for their ability to modulate the level of DR dimer formation. Incubation with the D₂R antagonist spiperone decreased the level of DR dimer formation significantly by 40-60% in real-time and after long-term (≥16 h) incubations. The fact that dimer formation of the well-studied A-DR dimer was not altered following incubation with spiperone supports the specificity of this observation. Other D₂R antagonists, such as clozapine, risperidone, and droperidol did not significantly evoke this dissociation event. Furthermore, molecular modeling reveals that spiperone presents specific Tyr199 and Phe390 conformations, compared to clozapine, which may determine D₂R homodimerization.
Topics: Clozapine; Dimerization; Dopamine D2 Receptor Antagonists; Humans; Protein Binding; Receptors, Dopamine D2; Receptors, G-Protein-Coupled; Spiperone
PubMed: 30987329
DOI: 10.3390/ijms20071686 -
Drug Design, Development and Therapy 2016Delivery of drug admixtures by intravenous patient-controlled analgesia is a common practice for the management of postoperative pain; however, analytical confirmation...
BACKGROUND
Delivery of drug admixtures by intravenous patient-controlled analgesia is a common practice for the management of postoperative pain; however, analytical confirmation of the compatibility and stability of butorphanol tartrate, ketamine hydrochloride, and droperidol combined in ternary admixtures is not available.
METHODS
Butorphanol tartrate, ketamine hydrochloride, and droperidol have been examined for compatibility and stability when combined with 0.9% sodium chloride injection stored at 4°C and 25°C with light protection for a total of 14 days. Concentrations were 0.067 mg/mL, 1.33 mg/mL, and 0.033 mg/mL for butorphanol tartrate, ketamine hydrochloride, and droperidol, respectively. Drug concentrations were determined using high-performance liquid chromatographic analysis.
RESULTS
All three drugs were very stable (>97%) at 4°C and 25°C for 14 days. The ternary admixtures were initially clear and colorless throughout the observation period, and the pH value did not change significantly.
CONCLUSION
The results confirm that the ternary admixture of butorphanol tartrate 0.067 mg/mL, ketamine hydrochloride 1.33 mg/mL, and droperidol 0.033 mg/mL in 0.9% sodium chloride injection were stable for 14 days when stored in polyolefin bags at 4°C and 25°C and protected from light.
Topics: Analgesia, Patient-Controlled; Analgesics; Butorphanol; Calibration; Chromatography, High Pressure Liquid; Droperidol; Drug Combinations; Drug Packaging; Drug Stability; Ketamine; Polyenes
PubMed: 27920502
DOI: 10.2147/DDDT.S123411 -
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 -
Parecoxib Reduced Postsurgical Pain and Facilitated Movement More Than Patient Controlled Analgesia.Frontiers in Surgery 2022Postoperative pain management is an imperative issue for patients undergoing lumbar spinal fusion surgery. Delayed pain relief is associated with poor clinical outcomes....
BACKGROUND
Postoperative pain management is an imperative issue for patients undergoing lumbar spinal fusion surgery. Delayed pain relief is associated with poor clinical outcomes. This study compared the effects of intravenously administered patient-controlled analgesia (PCA) with intravenous parecoxib, both commonly used methods for analgesic pain control after surgery.
METHODS
A non-randomized study was used to recruit 68 patients who were scheduled to receive lumbar spinal fusion surgery at a hospital in Taiwan from April through December of 2020. The group treated with parecoxib received an initial perioperative dose of parecoxib 40 mg during a 30-min period and then postoperative intravenous parecoxib at 40 mg per 12-h period, for 72 h. Those with PCA received morphine (0.4 mg/ml), droperidol (0.02 mg/ml), diphenhydramine (0.48 mg/ml), midazolam (0.02 mg/ml) and saline solution during the 3-day study course. Major outcomes, including visual scale pain score and Barthel index of activities of daily living, were collected via review of medical records at 4 times: 12, 24, 48 and 72 h after surgery. Comparative effects between two groups were assessed by the generalized estimating equations.
RESULTS
After adjusting for potential confounders, the administration of parecoxib was associated with a significant decrease in pain scores and an increase in the Barthel Index, when compared with the PCA group (all < 0.05). Notably, both effects would maintain for 72 h after surgery.
DISCUSSION
This is the first trial of which the authors are aware, that supports intravenous parecoxib as significantly enhancing patient mobility, in addition to having pain control efficacy, when compared with PCA. This study could be used as a reference when instituting interventions to improve the adaptation process and clinical prognoses after lumbar spinal fusion surgery.
PubMed: 35465430
DOI: 10.3389/fsurg.2022.799795 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Mar 2020To explore risk factors for postoperative nausea and vomiting (PONV) that requires intervention with medications during adolescent idiopathic scoliosis (AIS) surgery.
OBJECTIVE
To explore risk factors for postoperative nausea and vomiting (PONV) that requires intervention with medications during adolescent idiopathic scoliosis (AIS) surgery.
METHODS
We analyzed the data of 986 patients with AIS (including 156 male and 830 female patients) undergoing scoliosis surgery through a posterior approach between December, 2012 and January, 2016 in Nanjing Drum Tower Hospital. The data were collected from the patients including ASA grade, body mass index (BMI), Cobb angle, preoperative respiratory and cardiovascular diseases, operation time, type of anesthesia, quantity of intraoperative liquid infusion, blood loss, urine volume, the lowest MAP and CVP, intraoperative fentanyl consumption, and intraoperative administration of dexmedetomidine, dexamethasone, ondansetran and droperidol. The incidence of PONV in 48 h following the surgery, hemoglobin variation after operation (ΔHb), postoperative analgesia, times of use and types of antiemetic drugs, and postoperative hospital stay were recorded for all the patients. The potential risk factors of PONV within 48 h were analyzed using univariate analysis and multivariate logistic regression.
RESULTS
Of the 986 patients analyzed, 151 (15.3%) experienced PONV within 48 h following surgeries for AIS. Multivariate logistic regression analysis suggested that an high intraoperative fentanyl dose (> 0.65 mg; OR=9.303, 95% : 2.373-8.622, < 0.001), an obvious ΔHb (> 28.5 g/L; OR=1.107, 95% : 1.060-1.157, < 0.001), and postoperative analgesia with fentanyl (OR=11.671, 95% : 2.381-11.284, < 0.001) were risk factors for PONV. Intraoperative administration of dexmedetomidine (OR=0.027, 95% : 0.006-0.123, =0.002) and dexamethasone combined with ondansetron (OR=0.241, 95%: 0.066-0.886, =0.032) were protective factors against PONV.
CONCLUSIONS
A high-dose intraoperative fentanyl consumption, a marked ΔHb, and postoperative analgesia with fentanyl are risk factors for PONV while intraoperative administration of dexmedetomidine and dexamethasone combined with ondansetron are protective factors against PONV following surgeries for AIS.
Topics: Adolescent; Antiemetics; Double-Blind Method; Female; Humans; Male; Nausea; Ondansetron; Postoperative Nausea and Vomiting; Risk Factors; Scoliosis; Vomiting
PubMed: 32376591
DOI: 10.12122/j.issn.1673-4254.2020.03.18