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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 -
Frontiers in Pharmacology 2023Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In... (Review)
Review
Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In patients who developed PONV despite antiemetic prophylaxis, giving a rescue treatment from the same class of medication is known to be of limited efficacy. Given the widespread use of 5-HT3 antagonists as PONV prophylaxis, another class of effective intravenous rescue antiemetic is in dire need, especially when prophylaxis fails, and rescue medication is utilized. Dopamine antagonists were widely used for the treatment of PONV but have fallen out of favor due to some of their side effect profiles. Amisulpride was first designed as an antipsychotic medication but was found to have antiemetic properties. Here we will review the historical perspective on the use of dopamine receptor antagonist antiemetics, as well as the evidence on the efficacy and safety of amisulpride.
PubMed: 38026950
DOI: 10.3389/fphar.2023.1274214 -
BMC Anesthesiology Oct 2023There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to...
BACKGROUND
There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA.
METHODS
Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).
RESULTS
After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35-0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41-0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups.
CONCLUSIONS
The addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.
Topics: Humans; Antiemetics; Droperidol; Postoperative Nausea and Vomiting; Morphine; Cohort Studies; Retrospective Studies; Analgesia, Patient-Controlled; Propensity Score; Double-Blind Method
PubMed: 37898746
DOI: 10.1186/s12871-023-02319-2 -
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 -
Journal of Anesthesia Dec 2023Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently...
PURPOSE
Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently limited to its sedative and antiemetic effects. We investigated the effects of high and low doses of droperidol on the shivering threshold in rabbits.
METHODS
Forty-two male Japanese white rabbits were anesthetized with isoflurane and randomly assigned to the control, high-dose, or low-dose group. Rabbits in the high-dose group received a 5 mg/kg droperidol bolus followed by continuous infusion at 5 mg/kg/h, those in the low-dose group received a 0.5 mg/kg droperidol bolus, and those in the control group received the same volume of saline as the high-dose group. Body temperature was reduced at a rate of 2-3 °C/h, and the shivering threshold was defined as the subject's core temperature (°C) at the onset of shivering.
RESULTS
The shivering thresholds in the control, high-dose, and low-dose groups were 38.1 °C ± 1.1 °C, 36.7 °C ± 1.2 °C, and 36.9 °C ± 1.0 °C, respectively. The shivering thresholds were significantly lower in the high-dose and low-dose groups than in the control group (P < 0.01). The thresholds were comparable between the high-dose and low-dose groups.
CONCLUSIONS
Droperidol in high and low doses effectively reduced the shivering threshold in rabbits. Droperidol has been used in low doses as an antiemetic. Low doses of droperidol can reduce the incidence of shivering perioperatively and during the induction of therapeutic hypothermia.
Topics: Animals; Rabbits; Male; Shivering; Droperidol; Body Temperature; Isoflurane; Hypothermia
PubMed: 37566231
DOI: 10.1007/s00540-023-03240-1 -
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 -
Cureus Jun 2023Introduction Headaches are a common presentation to the emergency department, representing approximately 3% of visits. The standard treatment of headaches has consisted...
Introduction Headaches are a common presentation to the emergency department, representing approximately 3% of visits. The standard treatment of headaches has consisted of either monotherapy with an antidopaminergic agent or combination therapy with an antidopaminergic agent, a non-steroidal anti-inflammatory drug (NSAID), and diphenhydramine. Although droperidol is an antidopaminergic medication, it previously was not widely used in the treatment of headaches due to safety concerns. Given its pharmacokinetics, droperidol may provide faster relief in migrainous headaches compared to more commonly used antidopaminergic agents. Methods We conducted a single-center retrospective chart review to examine the impact of droperidol compared to other standard migraine therapies on pain scores. The study consisted of three treatment arms: droperidol monotherapy, a droperidol bundle (droperidol and ketorolac), and a prochlorperazine bundle (prochlorperazine and ketorolac). Patients who received medications in treatment arms and who had an encounter diagnosis including either "headache" or "migraine" were included. Patients were excluded if under 18 years of age, imprisoned, pregnant, or received potentially migraine-altering medications prior to the first documented pain score. The primary outcome was a mean reduction in pain scores. Secondary outcomes included length of emergency department stay, rates of inpatient admission, need for rescue therapies, and adverse events. Results A total of 361 droperidol orders were reviewed, of which 79 met the inclusion criteria. Of those included, 30 orders were within the droperidol monotherapy arm, 19 were within the droperidol bundle arm, and 30 were within the prochlorperazine bundle arm. There were no significant differences in reduction of pain scores, emergency department length of stay, rates of inpatient admission, rates of rescue therapy, or adverse events between the three treatment arms. Conclusion In this study, we found no statistical difference in migraine treatment efficacy between droperidol monotherapy and droperidol and prochlorperazine-based bundle therapies. Further studies are needed with larger sample sizes and predefined timing between pain score charting and medication administration.
PubMed: 37404431
DOI: 10.7759/cureus.39848 -
Academic Emergency Medicine : Official... May 2024Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct... (Review)
Review
BACKGROUND
Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct evidence on the effectiveness of capsaicin and dopamine antagonists in its clinical management.
METHODS
A bibliographic search was conducted to address the following population-intervention-control-outcome (PICO) question: (P) adults >18 years old with a diagnosis of acute CHS presenting to the ED; (I) dopamine antagonists (e.g., haloperidol, droperidol) and topical capsaicin; (C) usual care or no active comparator; and (O) symptoms improvement/resolution in ED, ED length of stay, admission rate, ED recidivism, need for rescue medication, and adverse events. This systematic review was conducted in accordance with PRISMA reporting recommendations.
RESULTS
From 53 potentially relevant articles, seven articles were included: five observational studies and two randomized controlled trials, including a total of 492 patients. Five of these studies evaluated the efficacy of capsaicin cream (n = 386), and two examined dopamine antagonists (haloperidol, droperidol; n = 106). There was mixed evidence for the efficacy of capsaicin for reducing nausea and emesis. Both studies evaluating dopamine antagonists detected clinical benefit to usual care or no active comparator.
CONCLUSIONS
There is limited direct evidence on the efficacy of dopamine antagonists or capsaicin for treating CHS in the ED. Current evidence is mixed for capsaicin and potentially beneficial for dopamine antagonists. Because of the small number of studies, small number of participants, lack of standardization of treatment administration, and risk of bias of the included studies, methodologically rigorous trials on both types of intervention are needed to directly inform ED management of CHS.
Topics: Humans; Vomiting; Emergency Service, Hospital; Capsaicin; Dopamine Antagonists; Administration, Topical; Adult; Antiemetics; Syndrome; Female; Male; Cannabinoid Hyperemesis Syndrome
PubMed: 37391387
DOI: 10.1111/acem.14770 -
Molecular Diversity Jun 2023Tyrosine Kinase beta (TRKβ), is a type I membrane receptor which plays a major role in various signalling pathways. TRKβ was found to be upregulated in various cancers...
Tyrosine Kinase beta (TRKβ), is a type I membrane receptor which plays a major role in various signalling pathways. TRKβ was found to be upregulated in various cancers and contrastingly downregulated in various neurodegenerative disorders. Hitherto, contemporary drug research is oriented towards discovery of TRKβ inhibitors, thus neglecting the development of TRKβ agonists. This research is aimed at identifying FDA approved drugs exhibiting repurposable potential as TRKβ agonists by mapping them with fingerprints of the BDNF/TRKβ interaction interface. Initially, crucial interacting residues were retrieved and a receptor grid was generated around it. TRKβ agonists were retrieved from literature search and a drug library was created for each agonist based on its structural and side effect similarities. Subsequently, molecular docking and dynamics were performed for each library to identify the drugs possessing affinity towards the binding pocket of TRKβ. The study revealed molecular interactions of Perospirone, Droperidol, Urapidil, and Clobenzorex with the crucial amino acids lining the active binding pocket of TRKβ. Subsequent network pharmacological analysis of the above drugs revealed their interactions with key proteins involved in neurotransmitter signalling pathways. Clobenzorex displayed high stability in dynamics simulation and therefore this drug is recommended for further experimental evaluations to attain better mechanistic insights and predict its implications in correcting neuropathological aberrations. This study's focus on the interaction interface between TRKβ and BDNF, combined with the utilization of fingerprint analysis for drug repurposing, contributes to our understanding of neurotrophic signalling and holds potential for identifying new therapeutic options for neurological disorders.
PubMed: 37389778
DOI: 10.1007/s11030-023-10673-z -
Pediatrics Jul 2023Pediatric mental health emergency department (ED) visits are rising in the United States, with more visits involving medication for acute agitation. Timely, standardized...
BACKGROUND AND OBJECTIVES
Pediatric mental health emergency department (ED) visits are rising in the United States, with more visits involving medication for acute agitation. Timely, standardized implementation of behavioral strategies and medications may reduce the need for physical restraint. Our objective was to standardize agitation management in a pediatric ED and reduce time in physical restraints.
METHODS
A multidisciplinary team conducted a quality improvement initiative from September 2020 to August 2021, followed by a 6-month maintenance period. A barrier assessment revealed that agitation triggers were inadequately recognized, few activities were offered during long ED visits, staff lacked confidence in verbal deescalation techniques, medication choices were inconsistent, and medications were slow to take effect. Sequential interventions included development of an agitation care pathway and order set, optimization of child life and psychiatry workflows, implementation of personalized deescalation plans, and adding droperidol to the formulary. Measures include standardization of medication choice for severe agitation and time in physical restraints.
RESULTS
During the intervention and maintenance periods, there were 129 ED visits with medication given for severe agitation and 10 ED visits with physical restraint use. Among ED visits with medication given for severe agitation, standardized medication choice (olanzapine or droperidol) increased from 8% to 88%. Mean minutes in physical restraints decreased from 173 to 71.
CONCLUSIONS
Implementing an agitation care pathway standardized and improved care for a vulnerable and high-priority population. Future studies are needed to translate interventions to community ED settings and to evaluate optimal management strategies for pediatric acute agitation.
Topics: Humans; Child; United States; Droperidol; Quality Improvement; Psychomotor Agitation; Emergency Service, Hospital; Restraint, Physical
PubMed: 37317809
DOI: 10.1542/peds.2022-059586