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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 -
Anesthesia Progress Sep 2020
Topics: Droperidol; Humans; Postoperative Nausea and Vomiting
PubMed: 32992339
DOI: 10.2344/anpr-67-03-14 -
British Journal of Clinical Pharmacology Dec 2016Intramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular...
BACKGROUND
Intramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular droperidol in these patients to determine how rapidly it is absorbed and the expected duration of measurable drug concentrations.
METHODS
We undertook a population pharmacokinetic analysis of a subgroup of patients from a clinical trial comparing droperidol and midazolam: 17 receiving 5 mg and 24 receiving 10 mg droperidol. Droperidol was measured using high-performance liquid chromatography. Pharmacokinetic modelling was performed under a nonlinear mixed effects modelling framework (NONMEM v7.2). The model was used to simulate concentration time profiles of three typical doses, 5 mg, 10 mg and 10 mg + 10 mg repeated at 15 min.
RESULTS
A two-compartment first-order input with first-order output model fitted the data best. The absorption rate constant was poorly characterised by the data and an estimate of the first order rate constant of absorption when fixed to 10 h provided a stable model and lowest objective function. This represents extremely rapid absorption with a half-life of 5 min. The final model had a clearance of 41.9 l h and volume of distribution of the central compartment of, 73.6 l. Median and interquartile range of initial (alpha) half-life was 0.32 h (0.26-0.37 h) and second (beta) half-life was 3.0 h (2.5-3.6 h). Simulations indicate that 10 mg alone provides an 80% probability of being above the lower limit of quantification (5 μg l ) for 7 h, 2 h longer than for 5 mg. Giving two 10 mg doses increased this duration to 10 h.
CONCLUSIONS
Intramuscular droperidol is rapidly absorbed with high therapeutic concentrations after 5 and 10 mg doses, and supports clinical data in which droperidol sedates rapidly for up to 6 h.
Topics: Absorption, Physiological; Adult; Antipsychotic Agents; Computer Simulation; Droperidol; Female; Half-Life; Humans; Injections, Intramuscular; Male; Models, Biological; Predictive Value of Tests; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 27530285
DOI: 10.1111/bcp.13093 -
Archives of Medical Science : AMS Apr 2015Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of...
INTRODUCTION
Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of combination therapy with ondansetron plus droperidol versus monotherapy with each agent alone in preventing postoperative nausea and vomiting following elective laparoscopic cholecystectomy.
MATERIAL AND METHODS
One hundred twenty-seven patients who underwent elective laparoscopic cholecystectomy under general anesthesia were included in the study, and assigned to one of the following three groups according to the antiemetic drug given intravenously at the end of the surgery: droperidol 1.25 mg in group D, ondansetron 4 mg in group O, and a combination of droperidol and ondansetron at the doses mentioned above in group D + O. Incidence of postoperative nausea and vomiting, and doses of given rescue antiemetics were recorded during the first postoperative day. The total drug cost per patient spent for postoperative nausea and vomiting management (including prophylactic antiemetics plus rescue postoperative antiemetics) was calculated.
RESULTS
Combination therapy significantly reduced postoperative nausea and vomiting at 30 min, 3 h and 6 h after surgery compared with group D (p < 0.01 for all time points) and O (p < 0.01 at 30 min, p < 0.05 at 3 h) and required less rescue antiemetic treatment (p < 0.01). Total antiemetic cost analyses revealed no significant differences among the three groups (p > 0.05).
CONCLUSIONS
Pretreatment with ondansetron plus droperidol is more effective than monotherapy in preventing postoperative nausea and vomiting following laparoscopic cholecystectomy, without increasing the cost comparatively.
PubMed: 25995753
DOI: 10.5114/aoms.2015.50968 -
The American Journal of Emergency... Feb 2022To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the... (Observational Study)
Observational Study
OBJECTIVE
To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department.
METHODS
Prospective cohort study of patients aged ≥12 years of age who received low-dose droperidol (≤ 2.5 mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc ≥ 500 ms after droperidol, delta ≥ +60 ms, and incidence of clinical adverse events. Patients were monitored up to 30 min after IV bolus and up to 46 min after infusion.
RESULTS
A total of 68 patients were included (mean age 42.1 years, 66.2% females). The median dose of droperidol was 1.875 mg (range 0.625 mg, 2.5 mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n = 41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9 ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval ≥ 500 ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc ≥ +60 ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n = 9) had at least one non-serious adverse event including restlessness and/or anxiety.
CONCLUSION
The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500 msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low.
Topics: Adjuvants, Anesthesia; Adult; Antiemetics; Dose-Response Relationship, Drug; Droperidol; Emergency Service, Hospital; Female; Humans; Long QT Syndrome; Male; Prospective Studies; Young Adult
PubMed: 34959024
DOI: 10.1016/j.ajem.2021.12.039 -
International Immunopharmacology Aug 2023Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms...
Postoperative cognitive dysfunction (POCD) is a decline in cognitive function affecting the mental health of aged patients after surgery. The pathological mechanisms underlying POCD have not yet been clarified. The overexpression of the P2X4 receptor in the central nervous system (CNS) was reported to be associated with the onset of POCD. Fast green FCF (FGF), a widely used food dye, could decrease the expression of the P2X4 receptor in the CNS. This study aimed to explore whether FGF could prevent POCD via the down-regulation of CNS P2X4 receptor. Exploratory laparotomy under the anesthesia of fentanyl and droperidol was carried to establish an animal model of POCD in 10-12-months-olds mice. FGF significantly attenuated cognitive impairments and down-regulated the expression of the P2X4 receptor induced by surgery in mice. Moreover, the blockade of CNS P2X4 receptor by intrahippocampal injection of 5-BDBD induced cognitive-enhancing effects on POCD mice. In addition, the effects of FGF were abolished by ivermectin, which is a positive allosteric modulator of the P2X4 receptor. FGF also inhibited M1 polarization of microglia cells, decreased the phosphorylation of nuclear factor-κB (NF-κB), and reduced the production of pro-inflammatory cytokines. These results suggested that FGF produced anti-POCD cognitive-enhancing effects via down-regulation of the P2X4 receptor-associated neuroinflammation, providing a support that FGF might be a potential treatment for POCD.
Topics: Mice; Animals; Postoperative Cognitive Complications; Down-Regulation; Receptors, Purinergic P2X4; Cognitive Dysfunction
PubMed: 37301120
DOI: 10.1016/j.intimp.2023.110462 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2022Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical...
OBJECTIVE
Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose.
METHODS
We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database.
RESULTS
There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; = 0.040), develop coma (16 [9%] vs. none; = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180-4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3-18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12-31 h; = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia.
CONCLUSION
Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.
Topics: Acetaminophen; Adult; Antidepressive Agents; Arrhythmias, Cardiac; Coma; Diazepam; Droperidol; Drug Overdose; Duloxetine Hydrochloride; Female; Humans; Hypotension; Ibuprofen; Middle Aged; Norepinephrine; Oxycodone; Pregabalin; Quetiapine Fumarate; Seizures; Serotonin; Sympathomimetics; Tachycardia
PubMed: 35658766
DOI: 10.1080/15563650.2022.2083631 -
Annals of Emergency Medicine Jan 2018
Topics: Aggression; Droperidol; Humans; Psychomotor Agitation; Psychotic Disorders
PubMed: 28662911
DOI: 10.1016/j.annemergmed.2017.05.005 -
The American Journal of Emergency... Jul 2023Acute agitation and violent behavior in the emergency department (ED) can lead to significant patient morbidity and contribute to the growing problem of workplace... (Observational Study)
Observational Study
PURPOSE
Acute agitation and violent behavior in the emergency department (ED) can lead to significant patient morbidity and contribute to the growing problem of workplace violence against health care providers. To our knowledge, there is no available literature directly comparing intramuscular ketamine to intramuscular droperidol in ED patients presenting with undifferentiated agitation. The purpose of this investigation was to compare the effectiveness and safety of these agents for acute agitation in the ED.
METHODS
This was a retrospective observational study conducted at an urban, academic ED. The primary endpoint was time from the first dose of study medication to restraint removal. Safety endpoints included incidence of bradycardia (heart rate < 60 bpm), hypotension (systolic blood pressure < 90 mmHg), hypoxia (oxygen saturation < 90% or need for respiratory support), and incidence of intubation for ongoing agitation or respiratory failure.
RESULTS
An initial 189 patients were screened, of which, 92 met inclusion criteria. The median time from initial drug administration to restraint removal was 49 min (IQR 30, 168) in the ketamine group and 43 min (IQR 30, 80) in the droperidol group (Median difference 6 min; 95% CI [-7, 26]). There was no significant difference in rates of bradycardia (3% vs 3%, 95% CI [-7%, 8%]), hypotension (0% vs 2%, 95% CI [-5%, 2%]), or hypoxia (7% vs 10%, 95% CI [-15%, 9%]) in the ketamine versus droperidol groups respectively. One patient in the ketamine group was intubated for ongoing agitation, and one patient in the droperidol group was intubated for respiratory failure.
CONCLUSIONS
Intramuscular droperidol and intramuscular ketamine were associated with similar times from drug administration to restraint removal in patients presenting to the ED with undifferentiated agitation. Prospective studies are warranted to evaluate IM droperidol and IM ketamine head-to-head as first line agents for acute agitation in the ED.
Topics: Humans; Droperidol; Ketamine; Retrospective Studies; Bradycardia; Psychomotor Agitation; Emergency Service, Hospital; Respiratory Insufficiency
PubMed: 37031618
DOI: 10.1016/j.ajem.2023.03.058 -
European Journal of Anaesthesiology Dec 2018Akathisia, a distressing movement disorder induced by butyrophenones, has been described with low doses of droperidol used for postoperative nausea and vomiting (PONV)... (Randomized Controlled Trial)
Randomized Controlled Trial
Incidence of akathisia after postoperative nausea and vomiting prophylaxis with droperidol and ondansetron in outpatient surgery: A multicentre controlled randomised trial.
BACKGROUND
Akathisia, a distressing movement disorder induced by butyrophenones, has been described with low doses of droperidol used for postoperative nausea and vomiting (PONV) prophylaxis, but the incidence remains unclear.
OBJECTIVES
To determine the incidence of akathisia after PONV prophylaxis with two doses of droperidol in comparison with ondansetron, in patients undergoing ambulatory surgery. We hypothesised that the incidence of akathisia is higher with droperidol than that with ondansetron.
DESIGN
Randomised controlled double blind trial.
SETTING
Two University Hospital Centres and two private Clinics from January to September 2014.
PATIENTS
Patients (n=297) undergoing general anaesthesia for ambulatory surgery were randomly allocated to receive PONV prophylaxis with droperidol (0.625 or 1.25 mg) or ondansetron 4 mg; patients of the three groups also received 4 mg of dexamethasone. Exclusion criteria were contraindication to droperidol and ondansetron, use of psychotropic medications or benzodiazepines or history of psychotic illness.
INTERVENTIONS
Participants received droperidol (0.625 or 1.25 mg) or ondansetron 4 mg during general anaesthesia. After discharge from the postanaesthesia care unit presence and severity of akathisia were assessed using the Barnes Akathisia Rating Scale at 4 h postoperatively.
MAIN OUTCOME MEASURES
Score of the Global Clinical Assessment of Akathisia of Barnes Akathisia Rating Scale.
RESULTS
The number of akathisia observed was 1/118 (0.8%) in the ondansetron group, 1/84 (1.2%) in droperidol 0.625 mg group, and 3/87 (3.4%) in droperidol 1.25 mg group. The akathisia rate difference among the three groups was not significant (P = 0.52). We could not demonstrate significant differences in the incidence of akathisia between the two doses of droperidol. The only case of marked akathisia treated with benzodiazepines was observed after droperidol 1.25 mg.
CONCLUSION
The use of droperidol or ondansetron for PONV prophylaxis is associated to a low incidence of akathisia (0.8 to 3.4%) after general anaesthesia for ambulatory surgery.
TRIAL REGISTRATION
Clinicaltrials.gov: NCT01942343.
Topics: Adult; Akathisia, Drug-Induced; Ambulatory Surgical Procedures; Antiemetics; Double-Blind Method; Droperidol; Female; Humans; Incidence; Male; Middle Aged; Ondansetron; Post-Exposure Prophylaxis; Postoperative Nausea and Vomiting
PubMed: 29746373
DOI: 10.1097/EJA.0000000000000821