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Anaesthesia Oct 2019We randomly allocated 50 women scheduled for radical mastectomy to pectoral nerves-2 (PECS-2) block (n = 25) or no block (n = 25), 20 and 22 of whom we analysed for... (Randomized Controlled Trial)
Randomized Controlled Trial
We randomly allocated 50 women scheduled for radical mastectomy to pectoral nerves-2 (PECS-2) block (n = 25) or no block (n = 25), 20 and 22 of whom we analysed for the primary outcome of a cumulative 24-h postoperative morphine dose. We gave intra-operative sufentanil, magnesium, dexamethasone and droperidol. Participants received regular postoperative paracetamol, ibuprofen and patient-controlled intravenous morphine. Pectoral nerves-2 block reduced mean (SD) cumulative 24 h postoperative morphine dose from 9.7 (8.9) mg to 5.0 (5.4) mg and 48 h morphine dose from 12.8 (12.5) mg to 6.0 (6.5) mg, p = 0.04 for both. The mean (SD) pain scores 24 h and 48 h after surgery were similar with or without block: 0.8 (1.4) vs. 1.2 (1.9), p = 0.39; and 0.2 (0.4) vs. 0.9 (1.8), p = 0.09, respectively. Rates of postoperative nausea, vomiting and pruritus were unaffected. Rates of chronic pain at six postoperative months were 2/19 and 2/18 after block and no block, respectively, p = 0.95.
Topics: Aged; Analgesics, Opioid; Breast Neoplasms; Female; Humans; Mastectomy, Radical; Middle Aged; Morphine; Nerve Block; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Prospective Studies; Pruritus; Thoracic Nerves; Treatment Outcome
PubMed: 31273773
DOI: 10.1111/anae.14769 -
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 -
The Journal of Veterinary Medical... Aug 2019The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period...
The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period as prognostic indicators in dogs. Data from 17 dogs which were scheduled to undergo elective craniotomy for brain tumor surgery from 2009 to 2012 were included. Of these, five (29.4%) died during 14 days after the surgery because of respiratory failure following pneumonia (n=2), euthanasia due to difficulty in treatment of status epilepticus (n=1), tumor-bed hematoma (n=1), and unknown reason (n=1). In the 12 surviving dogs, neurological signs were improved or resolved at discharge. All dogs were administered midazolam and droperidol-fentanyl as premedication. General anesthesia was induced using propofol maintained on isoflurane and oxygen. Direct ICP was obtained via a Codman Microsensor strain gauge transducer. ICP hypertension (>13 mmHg) measured after 15 min of recovery from the moment after discontinuation of anesthesia by turning off the vaporizer dial was associated with poor prognosis (odds ratio, 20.00; 95% confidence interval, 1.39-287.60, P=0.028). This suggests that intracranial pressure influences the postoperative mortality rate in dogs undergoing brain tumor surgery.
Topics: Anesthesia, General; Animals; Brain Neoplasms; Craniotomy; Dog Diseases; Dogs; Intracranial Hypertension; Postoperative Period; Prognosis
PubMed: 30982789
DOI: 10.1292/jvms.18-0475 -
Journal of Pain Research 2019Acute abdominal pain (AAP) comprises up to 10% of all emergency department (ED) visits. Current pain management practice is moving toward multi-modal analgesia regimens... (Review)
Review
BACKGROUND
Acute abdominal pain (AAP) comprises up to 10% of all emergency department (ED) visits. Current pain management practice is moving toward multi-modal analgesia regimens that decrease opioid use.
OBJECTIVE
This project sought to determine whether, in patients with AAP (population), does administration of butyrophenone antipsychotics (intervention) compared to placebo, usual care, or opiates alone (comparisons) improve analgesia or decrease opiate consumption (outcomes)?
METHODS
A structured search was performed in Cochrane CENTRAL, CINAHL, Database of Abstracts of Reviews of Effects, Directory of Open Access Journals, Embase, IEEE-Xplorer, Latin American and Caribbean Health Sciences Literature, Magiran, PubMed, Scientific Information Database, Scopus, TÜBİTAK ULAKBİM, and Web of Science. Clinical trial registries (ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and Australian New Zealand Clinical Trials Registry), relevant bibliographies, and conference proceedings were also searched. Searches were not limited by date, language, or publication status. Studies eligible for inclusion were prospective randomized clinical trials enrolling patients (age ≥18 years) with AAP treated in acute care environments (ED, intensive care unit, postoperative). The butyrophenone must have been administered either intravenously or intra-muscularly. Comparison groups included placebo, opiate only, corticosteroids, non-steroidal anti-inflammatory drugs, or acetaminophen.
RESULTS
We identified 7,217 references. Six studies met inclusion criteria. One study assessed ED patients with AAP associated with gastroparesis, whereas five studies assessed patients with postoperative AAP: abdominal hysterectomy (n=4), sleeve gastrectomy (n=1). Three of four studies found improvements in pain intensity with butyrophenone use. Three of five studies reported no change in postoperative opiate consumption, while two reported a decrease. One ED study reported no change in patient satisfaction, while one postoperative study reported improved satisfaction scores. Both extrapyramidal side effects (n=3) and sedation (n=3) were reported as unchanged.
CONCLUSION
Based on available evidence, we cannot draw a conclusion on the efficacy or benefit of neuroleptanalgesia in the management of patients with AAP. However, preliminary data suggest that it may improve analgesia and decrease opiate consumption.
PubMed: 30881092
DOI: 10.2147/JPR.S187798 -
Fujita Medical Journal 2019This study aimed to evaluate the effect of preventive administration of the combination of droperidol and dexamethasone on lowering the risk for postoperative nausea and...
Clinical evaluation of postoperative nausea and vomiting after cleft lip and/or palate surgery in pediatric patients. Part 2: evaluation of preventive administration of droperidol in combination with dexamethasone.
OBJECTIVES
This study aimed to evaluate the effect of preventive administration of the combination of droperidol and dexamethasone on lowering the risk for postoperative nausea and vomiting (PONV) after cleft-related surgery in pediatric patients.
METHODS
Preventive care consisted of a single dose of droperidol (0.025 mg/kg) and dexamethasone (0.06 mg/kg), which were administered at the end of surgery. The effect of preventive administration was evaluated in a sample group of 58 patients aged ≥3 years who underwent cleft-related surgery. Thirty patients received preventive administration (prevention group) and 28 patients did not (comparative group). The following outcome variables were evaluated between the groups: sex, age, body weight at the time of surgery, and duration of anesthesia. The presence or absence of PONV was the primary outcome and other variables were considered as explanatory variables.
RESULTS
The incidence rate of PONV was 20% (6/30) in the prevention group and 28.6% (8/28) in the comparative group, with no significant difference between the groups (p=0.45). In multiple logistic regression analysis, sex was the only explanatory factor of PONV, with a higher risk in girls than in boys (odds ratio, 6.20; 95% confidence interval, 1.65-27.63; p=0.01).
CONCLUSIONS
The incidence rate of PONV is 20% with preventive care of droperidol and dexamethasone administration, but this rate is not different from that without this combination. Sex is a risk factor for PONV. Further studies are required to validate our results.
PubMed: 35111502
DOI: 10.20407/fmj.2018-008 -
SAGE Open Medicine 2018Droperidol is used parenterally to treat nausea and vomiting, migraine and acute behavioural disturbance. Intranasal use is not reported for droperidol. Intranasal drug...
BACKGROUND
Droperidol is used parenterally to treat nausea and vomiting, migraine and acute behavioural disturbance. Intranasal use is not reported for droperidol. Intranasal drug administration reduces need for intravenous line placement and risk of needle-stick.
OBJECTIVE
To model population pharmacokinetics of intranasal droperidol.
METHOD
Single doses of intranasal and intravenous droperidol (0.02 mg/kg) were studied in an open-label crossover-trial in seven volunteers with a 1-week washout period. Blood samples collected over 10-h were analysed by liquid chromatography tandem mass spectrometer. Droperidol plasma concentrations following intravenous and intranasal administration were subjected to non-compartmental analysis and population pharmacokinetic modelling using S-ADAPT. Monte Carlo simulations were conducted for various potential intranasal dosage regimens.
RESULTS
The droperidol concentration-time profiles following intravenous and intranasal administration were best described by a model with two equilibrating disposition compartments and linear elimination. The apparent elimination clearance for intranasal dosing was 87.9 L/h and apparent central volume of distribution 18.2 L. Monte Carlo simulations of 5 mg droperidol (corresponding to the maximum volume that can be practically administered intranasal at a time) given intranasally at 0 and 5 min or 0 and 10 min indicated peak concentrations would reach those seen at 25 min after single intravenous administration of 1.5 mg. No adverse clinical effects or QT interval prolongation were observed.
CONCLUSION
Given the reduced bioavailability of intranasal droperidol, Monte Carlo simulations suggested that it could potentially be used at a higher dose (2.5-5 mg) than currently used intravenously in clinical trials assessing the effectiveness in treatment of nausea, vomiting and migraine.
PubMed: 30574300
DOI: 10.1177/2050312118813283 -
Academic Emergency Medicine : Official... Aug 2019The objective was to separately compare effectiveness of 1.25 mg of intravenous (IV) droperidol and 8 mg of IV ondansetron with 0.9% saline placebo for adult emergency... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The objective was to separately compare effectiveness of 1.25 mg of intravenous (IV) droperidol and 8 mg of IV ondansetron with 0.9% saline placebo for adult emergency department (ED) patients with nausea. A novel primary outcome measure, expected to aid clinical interpretation of reported results, was employed.
METHODS
A randomized controlled trial was conducted at the three EDs of Monash Health, Melbourne, Australia. The design was to demonstrate superiority of the active drugs over placebo. The primary outcome measure of symptom improvement was defined as a visual analog scale (VAS) rating change of -8 mm or more from baseline at 30 minutes posttreatment. Mean VAS changes per group and percentages experiencing the desired treatment effect were also compared. The study was concluded after recruitment of 215 of the planned 378 patients, as interim analysis confirmed that continuation could not result in a finding of superiority.
RESULTS
Of 215 patients, 73 (34%), 71 (33%), and 71 (33%) received droperidol, ondansetron, and placebo. Symptom improvement occurred in 75% (95% confidence interval [CI] = 64% to 85%), 80% (95% CI = 69% to 89%), and 76% (95% CI = 64% to 85%), respectively. Mean VAS changes were -29 mm (95% CI = -36 to -23 mm), -34 mm (95% CI = -41 to -28 mm), and -24 mm (95% CI = -29 to -19 mm), respectively. Desired treatment effects were experienced by 77% (95% CI = 65% to 86%), 73% (95% CI = 61% to 83%), and 59% (95% CI = 47% to 71%), respectively.
CONCLUSION
For adult ED patients with nausea, superiority was not demonstrated for droperidol or ondansetron over placebo.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Australia; Double-Blind Method; Droperidol; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Nausea; Ondansetron; Visual Analog Scale; Young Adult
PubMed: 30368981
DOI: 10.1111/acem.13650 -
Mediators of Inflammation 2018Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in...
Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in bleomycin-treated chimeric Thy1-deficient mice with wild-type lymphocytes that Thy1-deficient fibroblasts accumulate and promote fibrosis and an "inflammation-free" environment. Here, we aimed to identify the critical effects of Thy1, or the absence of Thy1, in lung myofibroblast profibrotic functions, particularly proliferation and collagen deposition. Using specific Thy1 siRNA in Thy1-positive cells, Thy1 knockout cells, Thy1 cDNA expression vector in Thy1-deficient cells, and Thy1 cross-linking, we evaluated cell proliferation (assessed by cell mass and BrdU uptake), differentiation (using immunofluorescence), and collagen deposition (using Sircol assay). We found that myofibroblast Thy1 cross-linking and genetic manipulation modulate cell proliferation and expression of Fgf (fibroblast growth factor) and Angtl (angiotensin) receptors (using qPCR) that are involved in myofibroblast proliferation, differentiation, and collagen deposition. In conclusion, lung myofibroblast downregulation of Thy1 expression is critical to increase proliferation, differentiation, and collagen deposition.
Topics: Animals; Bleomycin; Cell Cycle; Cell Proliferation; Cell Survival; Cells, Cultured; Droperidol; Flow Cytometry; Ketamine; Lung; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Myofibroblasts; Thy-1 Antigens
PubMed: 30002599
DOI: 10.1155/2018/4638437 -
Academic Emergency Medicine : Official... Jan 2019Acute agitation secondary to alcohol intoxication frequently requires parenteral sedatives for patient and caregiver safety. Antipsychotics play a prominent role;...
BACKGROUND
Acute agitation secondary to alcohol intoxication frequently requires parenteral sedatives for patient and caregiver safety. Antipsychotics play a prominent role; however, no consensus exists regarding the ideal agent. One important consideration when evaluating the choice of antipsychotic is its association with emergency department (ED) length of stay (LOS).
OBJECTIVES
We sought to determine the median ED LOS for patients receiving a single parenteral dose of an antipsychotic for acute agitation secondary to alcohol intoxication in an urban Level I trauma center.
METHODS
This was a retrospective review of patients receiving a single parenteral dose of droperidol, haloperidol, or olanzapine who were acutely intoxicated on alcohol from 2011 to 2016. Patients needing psychiatric assessment in our ED are discharged to a geographically separate department; thus, ED LOS is minimally impacted by waits for psychiatric assessment. Data were abstracted from the electronic medical record and are presented descriptively.
RESULTS
A total of 40,601 patients were identified and screened; 24,319 patients were intoxicated but received no sedation. Of those remaining 4,495 received multiple drugs and/or benzodiazepines leaving 11,787 for analysis. Median age was 42 years, 76% were male, and 5% of patients were admitted. Mean breath ethanol concentration was 227 mg/dL. Antipsychotics administered were as follows: droperidol (n = 3,790), haloperidol (n = 1,449), and olanzapine (n = 6,548). Median ED LOS was shortest for droperidol (499 minutes, 95% confidence interval [CI] = 493-506 minutes), which was significantly shorter than both haloperidol (524 minutes, 95% CI = 515-537 minutes) and olanzapine (533 minutes, 95% CI = 528-539 minutes). No cases of sudden cardiac death occurred.
CONCLUSION
Droperidol, when given as monotherapy for sedation of acute agitation secondary to alcohol intoxication, was associated with significantly shorter ED LOS than either parenteral haloperidol or parenteral olanzapine. No difference in ED LOS was observed between haloperidol and olanzapine.
Topics: Adult; Alcoholic Intoxication; Antipsychotic Agents; Droperidol; Drug Delivery Systems; Emergency Service, Hospital; Female; Haloperidol; Humans; Length of Stay; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Retrospective Studies
PubMed: 29851193
DOI: 10.1111/acem.13486 -
Ci Ji Yi Xue Za Zhi = Tzu-chi Medical... 2018Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United... (Review)
Review
Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United States Food and Drug Administration in 2001 because of a risk of development of torsades de pointes induced by QT prolongation. Many experts feel that the incidence of arrhythmia is overestimated, and low-dose droperidol is almost always used by anesthesiologists for postoperative nausea and vomiting. In this review, we used evidence-based analysis to appraise high-quality studies with a low risk of bias published after 2001 on the use of droperidol in the emergency department (ED). Droperidol appears not only efficacious but also safe to treat patients with nausea/vomiting, acute psychosis, and migraine in the ED. For these conditions, droperidol may be an option for shared decision-making.
PubMed: 29643708
DOI: 10.4103/tcmj.tcmj_195_17